Search

Magnetic resonance imaging (MRI) is the method of choice for noninvasive studies of micrometer-scale structures in biological tissues via their effects on the time- and frequency-dependent (restricted) and anisotropic self-diffusion of water. While new designs of time-dependent magnetic field gradient waveforms have enabled disambiguation between different aspects of translational motion that are convolved in traditional MRI methods relying on single pairs of field gradient pulses, data analysis for complex heterogeneous materials remains a challenge. Here, we propose and demonstrate nonparametric distributions of tensor-valued Lorentzian diffusion spectra, or "D(ω) distributions," as a general representation with sufficient flexibility to describe the MRI signal response from a wide range of model systems and biological tissues investigated with modulated gradient waveforms separating and correlating the effects of restricted and anisotropic diffusion. [ABSTRACT FROM AUTHOR]

Cyclic fluctuations in hypothalamic-pituitary-gonadal axis (HPG-axis) hormones exert powerful behavioral, structural, and functional effects through actions on the mammalian central nervous system. Yet, very little is known about how these fluctuations alter the structural nodes and information highways of the human brain. In a study of 30 naturally cycling women, we employed multidimensional diffusion and T1-weighted imaging during three estimated menstrual cycle phases (menses, ovulation, and mid-luteal) to investigate whether HPG-axis hormone concentrations co-fluctuate with alterations in white matter (WM) microstructure, cortical thickness (CT), and brain volume. Across the whole brain, 17β-estradiol and luteinizing hormone (LH) concentrations were directly proportional to diffusion anisotropy (μFA; 17β-estradiol: β1 = 0.145, highest density interval (HDI) = [0.211, 0.4]; LH: β1 = 0.111, HDI = [0.157, 0.364]), while follicle-stimulating hormone (FSH) was directly proportional to CT (β1 = 0 .162, HDI = [0.115, 0.678]). Within several individual regions, FSH and progesterone demonstrated opposing relationships with mean diffusivity (Diso) and CT. These regions mainly reside within the temporal and occipital lobes, with functional implications for the limbic and visual systems. Finally, progesterone was associated with increased tissue (β1 = 0.66, HDI = [0.607, 15.845]) and decreased cerebrospinal fluid (CSF; β1 = -0.749, HDI = [-11.604, -0.903]) volumes, with total brain volume remaining unchanged. These results are the first to report simultaneous brain-wide changes in human WM microstructure and CT coinciding with menstrual cycle-driven hormone rhythms. Effects were observed in both classically known HPG-axis receptor-dense regions (medial temporal lobe, prefrontal cortex) and in other regions located across frontal, occipital, temporal, and parietal lobes. Our results suggest that HPG-axis hormone fluctuations may have significant structural impacts across the entire brain.

Neurocognitive aging researchers are increasingly focused on the locus coeruleus, a neuromodulatory brainstem structure that degrades with age. With this rapid growth, the field will benefit from consensus regarding which magnetic resonance imaging (MRI) metrics of locus coeruleus structure are most sensitive to age and cognition. To address this need, the current study acquired magnetization transfer- and diffusion-weighted MRI images in younger and older adults who also completed a free recall memory task. Results revealed significantly larger differences between younger and older adults for maximum than average magnetization transfer-weighted contrast (MTC), axial than mean or radial single-tensor diffusivity (DTI), and free than restricted multi-compartment diffusion (NODDI) metrics in the locus coeruleus; with maximum MTC being the best predictor of age group. Age effects for all imaging modalities interacted with sex, with larger age group differences in males than females for MTC and NODDI metrics. Age group differences also varied across locus coeruleus subdivision for DTI and NODDI metrics, and across locus coeruleus hemispheres for MTC. Within older adults, however, there were no significant effects of age on MTC or DTI metrics, only an interaction between age and sex for free diffusion. Finally, independent of age and sex, higher restricted diffusion in the locus coeruleus was significantly related to better (lower) recall variability, but not mean recall. Whereas MTC has been widely used in the literature, our comparison between the average and maximum MTC metrics, inclusion of DTI and NODDI metrics, and breakdowns by locus coeruleus subdivision and hemisphere make important and novel contributions to our understanding of the aging of locus coeruleus structure.

The short association fibers or U-fibers travel in the superficial white matter (SWM) beneath the cortical layer. While the U-fibers play a crucial role in various brain disorders, there is a lack of effective tools to reconstruct their highly curved trajectory from diffusion MRI (dMRI). In this work, we propose a novel surface-based framework for the probabilistic tracking of fibers on the triangular mesh representation of the SWM. By deriving a closed-form solution to transform the spherical harmonics (SPHARM) coefficients of 3D fiber orientation distributions (FODs) to local coordinate systems on each triangle, we develop a novel approach to project the FODs onto the tangent space of the SWM. After that, we utilize parallel transport to realize the intrinsic propagation of streamlines on SWM following probabilistically sampled fiber directions. Our intrinsic and surface-based method eliminates the need to perform the necessary but challenging sharp turns in 3D compared with conventional volume-based tractography methods. Using data from the Human Connectome Project (HCP), we performed quantitative comparisons to demonstrate the proposed algorithm can more effectively reconstruct the U-fibers connecting the precentral and postcentral gyrus than previous methods. Quantitative validations were then performed on post-mortem MRIs to show the reconstructed U-fibers from our method more faithfully follow the SWM than volume-based tractography. Finally, we applied our algorithm to study the parietal U-fiber connectivity changes in autosomal dominant Alzheimers disease (ADAD) patients and successfully detected significant associations between U-fiber connectivity and disease severity.

BACKGROUND: Microvascular dysfunction is involved in the development of various cerebral disorders. It may contribute to these disorders by disrupting white matter tracts and altering brain connectivity, but evidence is scarce. We investigated the association between multiple biomarkers of microvascular function and whole-brain white matter connectivity. METHODS AND RESULTS: Cross-sectional data from The Maastricht Study, a Dutch population-based cohort (n=4326; age, 59.4±8.6 years; 49.7% women). Measures of microvascular function included urinary albumin excretion, central retinal arteriolar and venular calibers, composite scores of flicker light-induced retinal arteriolar and venular dilation, and plasma biomarkers of endothelial dysfunction (intercellular adhesion molecule-1, vascular cell adhesion molecule-1, E-selectin, and von Willebrand factor). White matter connectivity was calculated from 3T diffusion magnetic resonance imaging to quantify the number (average node degree) and organization (characteristic path length, global efficiency, clustering coefficient, and local efficiency) of white matter connections. A higher plasma biomarkers of endothelial dysfunction composite score was associated with a longer characteristic path length (β per SD, 0.066 [95% CI, 0.017-0.114]) after adjustment for sociodemographic, lifestyle, and cardiovascular factors but not with any of the other white matter connectivity measures. After multiple comparison correction, this association was nonsignificant. None of the other microvascular function measures were associated with any of the connectivity measures. CONCLUSIONS: These findings suggest that microvascular dysfunction as measured by indirect markers is not associated with whole-brain white matter connectivity.

Diffusion MRI (dMRI) can be used to probe microstructural properties of brain tissue and holds great promise as a means to non-invasively map Alzheimer's disease (AD) pathology. Few studies have evaluated multi-shell dMRI models such as neurite orientation dispersion and density imaging (NODDI) and mean apparent propagator (MAP)-MRI in cortical gray matter where many of the earliest histopathological changes occur in AD. Here, we investigated the relationship between CSF pTau181 and Aβ1-42 burden and regional cortical NODDI and MAP-MRI indices in 46 cognitively unimpaired individuals, 18 with mild cognitive impairment, and two with dementia (mean age: 71.8 ± 6.2 years) from the Alzheimer's Disease Neuroimaging Initiative. We compared findings to more conventional cortical thickness measures. Lower CSF Aβ1-42 and higher pTau181 were associated with cortical dMRI measures reflecting less hindered or restricted diffusion and greater diffusivity. Cortical dMRI measures, but not cortical thickness measures, were more widely associated with Aβ1-42 than pTau181 and better distinguished Aβ+ from Aβ- participants than pTau+ from pTau- participants. dMRI associations mediated the relationship between CSF markers and delayed logical memory performance, commonly impaired in early AD. dMRI metrics sensitive to early AD pathogenesis and microstructural damage may be better measures of subtle neurodegeneration in comparison to standard cortical thickness and help to elucidate mechanisms underlying cognitive decline.

BACKGROUND: Sensory processing dysfunction (SPD) is linked to altered white matter (WM) microstructure in school-age children. Sensory over-responsivity (SOR), a form of SPD, affects at least 2.5% of all children and has substantial deleterious impact on learning and mental health. However, SOR has not been well studied using microstructural imaging such as diffusion MRI (dMRI). Since SOR involves hypersensitivity to external stimuli, we test the hypothesis that children with SOR require compensatory neuroplasticity in the form of superior WM microstructural integrity to protect against internalizing behavior, leaving those with impaired WM microstructure vulnerable to somatization and depression. METHODS: Children ages 8-12 years old with neurodevelopmental concerns were assessed for SOR using a comprehensive structured clinical evaluation, the Sensory Processing 3 Dimensions Assessment, and underwent 3 Tesla MRI with multishell multiband dMRI. Tract-based spatial statistics was used to measure diffusion tensor imaging (DTI) and neurite orientation dispersion and density imaging (NODDI) metrics from global WM and nineteen selected WM tracts. Correlations of DTI and NODDI measures with measures of somatization and emotional disturbance from the Behavioral Assessment System for Children, 3rd edition (BASC-3), were computed in the SOR group and in matched children with neurodevelopmental concerns but not SOR. RESULTS: Global WM fractional anisotropy (FA) is negatively correlated with somatization and with emotional disturbance in the SOR group but not the non-SOR group. Also observed in children with SOR are positive correlations of radial diffusivity (RD) and free water fraction (FISO) with somatization and, in most cases, emotional disturbance. These effects are significant in boys with SOR, whereas the study is underpowered for girls. The most affected white matter are medial lemniscus and internal capsule sensory tracts, although effects of SOR are observed in many cerebral, cerebellar, and brainstem tracts. CONCLUSION: White matter microstructure is related to affective behavior in children with SOR.

BackgroundHigh b-value diffusion-weighted images (DWI) are used for detection of clinically significant prostate cancer (csPCa). This study qualitatively and quantitatively compares synthesized DWI (sDWI) to acquired (aDWI) for detection of csPCa.MethodsOne hundred fifty-one consecutive patients who underwent prostate MRI and biopsy were included in the study. Axial DWI with b = 0, 500, 1000, and 2000 s/mm2 using a 3T clinical scanner using a 32-channel phased-array body coil were acquired. We retrospectively synthesized DWI for b = 2000 s/mm2 via extrapolation based on mono-exponential decay, using b = 0 and b = 500 s/mm2 (sDWI500) and b = 0, b = 500 s/mm2, and b = 1000 s/mm2 (sDWI1000). Differences in signal intensity between sDWI and aDWI were evaluated within different regions of interest (prostate alone, prostate plus 5 mm, 30 mm and 70 mm margin and full field of view). The maximum DWI value within each ROI was evaluated for prediction of csPCa. Classification accuracy was compared to Restriction Spectrum Imaging restriction score (RSIrs), a previously validated biomarker based on multi-exponential DWI. Discrimination of csPCa was evaluated via area under the receiver operating characteristic curve (AUC).ResultsWithin the prostate, mean ± standard deviation of percent mean differences between sDWI and aDWI signal were -46 ± 35% for sDWI1000 and -67 ± 24% for sDWI500. AUC for aDWI, sDWI500, sDWI1000, and RSIrs within the prostate 0.62[95% confidence interval: 0.53, 0.71], 0.63[0.54, 0.72], 0.65[0.56, 0.73] and 0.78[0.71, 0.86], respectively.ConclusionsDWI is qualitatively comparable to aDWI within the prostate. However, hyperintense artifacts are introduced with sDWI in the surrounding pelvic tissue that interfere with quantitative cancer detection and might mask metastases. In the prostate, RSIrs yields superior quantitative csPCa detection than sDWI or aDWI.

Objectives: Using magnetic resonance imaging (MRI), we analysed the clinical manifestations of granulomatous lobular mastitis (GLM) before and after treatment with traditional Chinese medicine (TCM). Methods: This was a retrospective study. Clinical manifestations and imaging features of patients with biopsy-proven GLM before and after treatment were retrospectively analysed from April 2021 to April 2023 at Xiyuan Hospital, China Academy of Chinese Medical Sciences. Results: Among 29 women of childbearing age (mean age, 34.3±3.6 years), Compared to pre-therapy, the number of patients with lumps, ruptures, pain, and menstrual irregularities was significantly reduced (P < 0.05). The Chinese medicine staging demonstrated a transition from bulk to ulcerated (P=0.041). Pre- and post-treatment MRI changes included lesion number, distribution, maximal diameter, time-signal intensity curves (TIC), apparent diffusion coefficients (ADC), and BI-RADS categories 3 and 4a (all P<0.05). Furthermore, substantial changes were seen in chest wall invasion, nipple discharge, increased feeding arteries, and skin edema (all P<0.05). Conclusion: Combining internal and external Traditional Chinese Medicine (TCM) therapy proved successful for GLM. A reliable assessment of therapy efficacy is provided by MRI examination of lesion changes before and after treatment. [ABSTRACT FROM AUTHOR]

Objectives: To investigate associations between tissue diffusion, stiffness, and different tumor microenvironment features in resected hepatocellular carcinoma (HCC). Methods: Seventy-two patients were prospectively included for preoperative magnetic resonance (MR) diffusion-weighted imaging and MR elastography examination. The mean apparent diffusion coefficient (ADC) and stiffness value were measured on the central three slices of the tumor and peri-tumor area. Cell density, tumor-stroma ratio (TSR), lymphocyte-rich HCC (LR-HCC), and CD8 + T cell infiltration were estimated in resected tumors. The interobserver agreement of MRI measurements and subjective pathological evaluation was assessed. Variables influencing ADC and stiffness were screened with univariate analyses, and then identified with multivariable linear regression. The potential relationship between explored imaging biomarkers and histopathological features was assessed with linear regression after adjustment for other influencing factors. Results: Seventy-two patients (male/female: 59/13, mean age: 56 ± 10.2 years) were included for analysis. Inter-reader agreement was good or excellent regarding MRI measurements and histopathological evaluation. No correlation between tumor ADC and tumor stiffness was found. Multivariable linear regression confirmed that cell density was the only factor associated with tumor ADC (Estimate = −0.03, p = 0.006), and tumor-stroma ratio was the only factor associated with tumor stiffness (Estimate = −0.18, p = 0.03). After adjustment for fibrosis stage (Estimate = 0.43, p < 0.001) and age (Estimate = 0.04, p < 0.001) in the multivariate linear regression, intra-tumoral CD8 + T cell infiltration remained a significant factor associated with peri-tumor stiffness (Estimate = 0.63, p = 0.02). Conclusions: Tumor ADC surpasses tumor stiffness as a biomarker of cellularity. Tumor stiffness is associated with tumor-stroma ratio and peri-tumor stiffness might be an imaging biomarker of intra-tumoral immune microenvironment. Clinical relevance statement: Tissue stiffness could potentially serve as an imaging biomarker of the intra-tumoral immune microenvironment of hepatocellular carcinoma and aid in patient selection for immunotherapy. Key Points: Apparent diffusion coefficient reflects cellularity of hepatocellular carcinoma. Tumor stiffness reflects tumor-stroma ratio of hepatocellular carcinoma and is associated with tumor-infiltrating lymphocytes. Tumor and peri-tumor stiffness might serve as imaging biomarkers of intra-tumoral immune microenvironment. [ABSTRACT FROM AUTHOR]

Objectives: Telomerase reverse transcriptase promoter (pTERT) mutation status plays a key role in making decisions and predicting prognoses for patients with World Health Organization (WHO) grade IV glioma. This study was conducted to assess the value of diffusion-weighted imaging (DWI) for predicting pTERT mutation status in WHO grade IV glioma. Methods: MRI data and molecular information were obtained for 266 patients with WHO grade IV glioma at the hospital and divided into training and validation sets. The ratio of training to validation set was approximately 10:3. We trained the same residual convolutional neural network (ResNet) for each MR modality, including structural MRIs (T1-weighted, T2-weighted, and contrast-enhanced T1-weighted) and DWI*, to compare the predictive capacities between DWI and conventional structural MRI. We also explored the effects of different regions of interest on pTERT mutation status prediction outcomes. Results: Structural MRI modalities poorly predicted the pTERT mutation status (accuracy = 51%-54%; area under the curve [AUC]=0.545-0.571), whereas DWI combined with its apparent diffusive coefficient maps yielded the best predictive performance (accuracy = 85.2%, AUC = 0.934). Including the radiological and clinical characteristics did not further improve the performance for predicting pTERT mutation status. The entire tumour volume yielded the best prediction performance. Conclusions: DWI technology shows promising potential for predicting pTERT mutations in WHO grade IV glioma and should be included in the MRI protocol for WHO grade IV glioma in clinical practice. Advances in knowledge: This is the first large-scale model study to validate the predictive value of DWI for pTERT in WHO grade IV glioma. [ABSTRACT FROM AUTHOR]

Objectives: To compare prostate monoparametric MRI (monoMRI), which uses only diffusion-weighted imaging (DWI), with biparametric (bpMRI) and multiparametric MRI (mpMRI) in detecting clinically significant cancer (CSC) and to evaluate the effect of the combination of monoMRI results and prostate-specific antigen (PSA) level. Methods: In this study, 193 patients (average age 70.5 years; average PSA 7.9 ng/mL) underwent prebiopsy MRI and subsequent prostate biopsy from January 2020 to February 2022. Two radiologists independently reviewed the 3 MRI protocols using the Prostate Imaging Reporting and Data System (PI-RADS). Interreader agreement was assessed using the intraclass correlation coefficient (ICC), and diagnostic performance was evaluated with receiver operating characteristic (ROC) curve analysis. The Youden index was used to determine the new cutoff value of PSA for detecting CSCs in patients with negative monoMRI results. Results: CSC was confirmed in 109 patients (56.5%). The interreader agreement on monoMRI (ICC = 0.798) was comparable to that on bpMRI and mpMRI (ICC = 0.751 and 0.714, respectively). ROC curve analysis of the 3 protocols revealed no difference in detecting CSCs (P > 0.05). Applying a new PSA cutoff value (9.5 and 7.4 ng/mL, respectively) in monoMRI-negative patients improved the sensitivity of monoMRI from 89.9% to 96.3% for Reader 1, and from 95.4% to 99.1% for Reader 2. Conclusions: MonoMRI based solely on DWI demonstrated similar diagnostic performance to bpMRI and mpMRI in detecting CSCs, and the combination of PSA level with monoMRI has the potential to effectively triage patients with a high likelihood of CSCs. Advances in knowledge: Monoparametric MRI conducted only with diffusion-weighted imaging (DWI), may show comparable performance to biparametric and multiparametric MRI in detecting clinically significant prostate cancer. In patients with negative monoparametric MRI results, implementing a new PSA cutoff value to determine the need for a biopsy could decrease the number of missed prostate cancer. [ABSTRACT FROM AUTHOR]

Objective: Glymphatic system is a recently discovered macroscopic waste clearance system associated with numerous neurological diseases. However, little is known about glymphatic system development in neonates. We sought to evaluate diffusion along the perivascular space (ALPS) index, a proxy for glymphatic system function, in neonates and investigate its potential associations with maturation, sex, and preterm birth. Methods: Diffusion magnetic resonance imaging (MRI) data in 418 neonates, including 92 preterm neonates (57 males) and 326 term neonates (175 males), from the Developing Human Connectome Project were used for evaluating ALPS index. Linear regression modeling was performed to assess group differences in the ALPS index according to preterm birth and sex. Pearson's and partial correlation analysis were performed to assess the association between the ALPS index and gestational age (GA) as well as postmenstrual age (PMA) at MRI. Moderation analysis was performed to assess the moderation effect of preterm birth on the relationship between the ALPS index and PMA. Results: Compared to term neonates, preterm neonates exhibited lower ALPS indices (p < 0.001). The ALPS index positively correlated with PMA (p = 0.004) and GA (p < 0.001). Preterm birth (p = 0.013) had a significant moderation effect on the relationship between the ALPS index and PMA. Sex had no significant direct effect (p = 0.639) or moderation effect (p = 0.333) on ALPS index. Interpretation: Glymphatic system development is a dynamic process in neonates, which can be moderated by preterm birth, the ALPS index could serve as a sensitive biomarker for monitoring this process. ANN NEUROL 2024;96:970–980 [ABSTRACT FROM AUTHOR]

Chronic pain is common in young people and can have a major life impact. Despite the burden of chronic pain, mechanisms underlying chronic pain development and persistence are still poorly understood. Specifically, white matter (WM) connectivity has remained largely unexplored in pediatric chronic pain. Using diffusion-weighted imaging, this study examined WM microstructure in adolescents (age M 5 15.8 years, SD 5 2.8 years) with chronic pain (n 5 44) compared with healthy controls (n 5 24). Neurite orientation dispersion and density imaging modeling was applied, and voxel-based whole-white-matter analyses were used to obtain an overview of potential alterations in youth with chronic pain and tract-specific profile analyses to evaluate microstructural profiles of tracts of interest more closely. Our main findings are that (1) youth with chronic pain showed widespread elevated orientation dispersion compared with controls in several tracts, indicative of less coherence; (2) signs of neurite density tract-profile alterations were observed in several tracts of interest, with mainly higher density levels in patients; and (3) several WM microstructural alterations were associated with pain catastrophizing in the patient group. Implicated tracts include both those connecting cortical and limbic structures (uncinate fasciculus, cingulum, anterior thalamic radiation), which were associated with pain catastrophizing, as well as sensorimotor tracts (corticospinal tract). By identifying alterations in the biologically informative WM microstructural metrics orientation dispersion and neurite density, our findings provide important and novel mechanistic insights for understanding the pathophysiology underlying chronic pain. Taken together, the data support alterations in fiber organization as a meaningful characteristic, contributing process to the chronic pain state. [ABSTRACT FROM AUTHOR]

The editorial "Towards multi-modal, multi-species brain atlases: part two" discusses the era of big data in neuroanatomy, with advancements in data collection and analysis across various species. The article highlights challenges in sharing methods and results due to specialized techniques and terminology. It also emphasizes the importance of frameworks that integrate diverse data types and species. The special issue of Brain Structure and Function aims to bring together researchers working on these issues, showcasing contributions that range from connectivity blueprints to whole-brain atlases in different species. The article underscores the significance of comparative neuroanatomy in understanding brain organization and evolution. [Extracted from the article]

Diffusion MRI tractography (dMRI) has fundamentally transformed our ability to investigate white matter pathways in the human brain. While long-range connections have extensively been studied, superficial white matter bundles (SWMBs) have remained a relatively underexplored aspect of brain connectivity. This study undertakes a comprehensive examination of SWMB connectivity in both the human and chimpanzee brains, employing a novel combination of empirical and geometric methodologies to classify SWMB morphology in an objective manner. Leveraging two anatomical atlases, the Ginkgo Chauvel chimpanzee atlas and the Ginkgo Chauvel human atlas, comprising respectively 844 and 1375 superficial bundles, this research focuses on sparse representations of the morphology of SWMBs to explore the little-understood superficial connectivity of the chimpanzee brain and facilitate a deeper understanding of the variability in shape of these bundles. While similar, already well-known in human U-shape fibers were observed in both species, other shapes with more complex geometry such as 6 and J shapes were encountered. The localisation of the different bundle morphologies, putatively reflecting the brain gyrification process, was different between humans and chimpanzees using an isomap-based shape analysis approach. Ultimately, the analysis aims to uncover both commonalities and disparities in SWMBs between chimpanzees and humans, shedding light on the evolution and organization of these crucial neural structures. [ABSTRACT FROM AUTHOR]

Non-human primates are extensively used in neuroscience research as models of the human brain, with the rhesus macaque being a prominent example. We have previously introduced a set of tractography protocols (XTRACT) for reconstructing 42 corresponding white matter (WM) bundles in the human and the macaque brain and have shown cross-species comparisons using such bundles as WM landmarks. Our original XTRACT protocols were developed using the F99 macaque brain template. However, additional macaque template brains are becoming increasingly common. Here, we generalise the XTRACT tractography protocol definitions across five macaque brain templates, including the F99, D99, INIA, Yerkes and NMT. We demonstrate equivalence of such protocols in two ways: (a) Firstly by comparing the bodies of the tracts derived using protocols defined across the different templates considered, (b) Secondly by comparing the projection patterns of the reconstructed tracts across the different templates in two cross-species (human–macaque) comparison tasks. The results confirm similarity of all predictions regardless of the macaque brain template used, providing direct evidence for the generalisability of these tractography protocols across the five considered templates. [ABSTRACT FROM AUTHOR]

The recent development of methods for constructing directly comparable white matter atlases in primate brains from diffusion MRI allows us to probe specializations unique to humans, great apes, and other primate taxa. Here, we constructed the first white matter atlas of a lesser ape using an ex vivo diffusion-weighted scan of a brain from a young adult (5.5 years) male lar gibbon. We find that white matter architecture of the gibbon temporal lobe suggests specializations that are reminiscent of those previously reported for great apes, specifically, the expansion of the arcuate fasciculus and the inferior longitudinal fasciculus in the temporal lobe. Our findings suggest these white matter expansions into the temporal lobe were present in the last common ancestor to hominoids approximately 16 million years ago and were further modified in the great ape and human lineages. White matter atlases provide a useful resource for identifying neuroanatomical differences and similarities between humans and other primate species and provide insight into the evolutionary variation and stasis of brain organization. [ABSTRACT FROM AUTHOR]

To evaluate the diagnostic performance of diffusion-weighted imaging (DWI) and dynamic contrast enhanced (DCE), for diagnosing osteomyelitis in the diabetic foot. A thorough search was carried out to identify suitable studies published up to September 2023. The quality of the studies involved was evaluated using Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2). The diagnostic sensitivity and specificity of each imaging modality/method for each specific cut point were summarized. The summary receiver operating characteristic (SROC) curve was calculated using bivariate mixed effects models. Five studies investigating 187 patients and 234 bone lesions with 110 diagnosed osteomyelitis were enrolled. Four studies used DWI (172 lesions), three studies used DCE techniques (140 lesions) and two studies presented results of conventional MRI (66 lesions). The sensitivity ranges using conventional MRI, DWI and DCE were 65%-100%, 65%-100% and 64%-100%, respectively. The specificity ranges were 50%-61%, 56%-95%, and 66%-93%, respectively. The SROC curve of DWI and DCE was 0.89 (95% CI, 0.86–0.92) and 0.90 (95% CI, 0.87–0.92), respectively. Combining DWI and DCE methods, alongside conventional MRI, can improve the reliability and accuracy of diabetic foot osteomyelitis diagnosis. However, the study recognizes result variability due to varying protocols and emphasizes the need for well-designed studies with standardized approaches. To optimize diagnostic performance, the study recommends considering low ADC values, Ktrans or rapid wash-in rate from DCE such as iAUC60, along with using large ROIs that cover the entire lesion while excluding normal bone marrow. [ABSTRACT FROM AUTHOR]

Combining computed diffusion-weighted imaging (DWI) with readout-segmented echo-planar-imaging may shorten acquisition time and improve imaging quality. This study aimed to compare computed vs. acquired DWI qualitatively and quantitatively in visualizing scrotal or testicular lesions. We retrospectively enrolled 57 consecutive men who underwent scrotal MRI. Four computed DWI sets (cDWI 800 , cDWI 1000 , cDWI 1200 , and cDWI 1400) were generated from acquired DWI with two lower b-values (150 and 600 s/mm2). Acquired DWI (DWI 800 and DWI 1000) and computed DWI were compared through qualitative (susceptibility artifact, signal loss artifact, anatomic clarity, and lesion conspicuity) and quantitative assessment (signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), and lesion-to-testicular parenchyma contrast ratio (CR)). Computed DWI was prone to signal loss artifact and slightly lower assessment scores in terms of anatomic clarity and lesion conspicuity, comparing with acquired DWI. The SNR of computed and acquired DWI decreased with increasing b value. Under the same b-values (800 and 1,000 s/mm2), there was no difference in the median SNR and CR between computed and acquired DWI. The median CR of cDWI 1400 was significantly higher than that of the other DWI sets excepting cDWI 1200 (P =1.000). The median CNR tended to be lower for computed vs. acquired DWI, while no significant difference (P =0.233). Computed and acquired DWI were nearly equivalent in both qualitative and quantitative evaluations at the b values of 800 and 1,000 s/mm2. Computed DWI could enhance the contrast of scrotal or testicular lesions. • Computed vs. acquired DWI are equivalent at the b values of 800 and 1,000 s/mm2. • Computed DWI could enhance the contrast of scrotal or testicular lesions. • Computed DWI can serve visual aid to radiologists without increasing scan time. [ABSTRACT FROM AUTHOR]

The utility of the apparent diffusion coefficient (ADC) of diffusion-weighted image (DWI) magnetic resonance imaging was examined for evaluating malignancy and prognosis in gallbladder tumors. A total of 63 patients (benign tumors, n=33; cancer, n=30) were included after surgical resection for gallbladder tumors, and their mean ADC values by DWI were obtained. Cases of advanced gallbladder cancer (n=25) were divided into ADCHigh and ADCLow groups, and clinicopathological factors were compared. In 63 cases, ADC values in advanced gallbladder cancer were significantly lower compared with benign tumors and non-advanced gallbladder cancer (P<0.05), and ADC values in early gallbladder cancer were also significantly lower compared with benign tumors (P<0.05). In 25 advanced gallbladder cancer cases, the ADCLow group tended to have a higher rate of advanced stage disease (P=0.09). Disease-free survival and overall survival (OS) of the ADCLow group were worse compared with the ADCHigh group (P<0.01). In the multivariate analysis of OS, poor differentiation and low ADC value were independent prognostic factors. ADC values may be useful for evaluating tumor malignancies in gallbladder tumors. [ABSTRACT FROM AUTHOR]

This document discusses a case of a painless knee mass in a young adult. The MRI showed a soft tissue lesion in the posterior recess of the knee, closely related to the anterior cruciate ligament. A provisional diagnosis of a complex ACL ganglion was made based on the MRI findings. However, an aspiration biopsy revealed a synovial sarcoma, a rare and aggressive soft tissue sarcoma. The document emphasizes the importance of histopathological analysis in cases of ganglion aspiration to avoid misdiagnosis. The management of synovial sarcoma involves surgical resection and, in some cases, radiotherapy or neoadjuvant chemoradiotherapy. [Extracted from the article]

Apolipoprotein E ε4 (APOE4) is a strong genetic risk factor of Alzheimer's disease and metabolic dysfunction. However, whether APOE4 and markers of metabolic dysfunction synergistically impact the deterioration of white matter (WM) integrity in older adults remains unknown. In the UK Biobank data, we conducted a multivariate analysis to investigate the interactions between APOE4 and 249 plasma metabolites (measured using nuclear magnetic resonance spectroscopy) with whole-brain WM integrity (measured by diffusion-weighted magnetic resonance imaging) in a cohort of 1917 older adults (aged 65.0–81.0 years; 52.4 % female). Although no main association was observed between either APOE4 or metabolites with WM integrity (adjusted P > 0.05), significant interactions between APOE4 and metabolites with WM integrity were identified. Among the examined metabolites, higher concentrations of low-density lipoprotein and very low-density lipoprotein were associated with a lower level of WM integrity (b= − 0.12 , CI= − 0.14 , − 0.10 ) among APOE4 carriers. Conversely, among non-carriers, they were associated with a higher level of WM integrity (b=0.05, CI= 0.04,0.07 ), demonstrating a significant moderation role of APOE4 (b = − 0.18 , CI= − 0.20 , − 0.15 , P<0.00001). • LDL is negatively associated with white matter integrity in older APOE4 carriers. • This association, although weak, is positive in APOE4 non-carriers. • APOE4 carriers with high LDL show a stronger negative age-cognition correlation. [ABSTRACT FROM AUTHOR]

Filter exchange imaging (FEXI) is a double diffusion‐encoding (DDE) sequence that is specifically sensitive to exchange between sites with different apparent diffusivities. FEXI uses a diffusion‐encoding filtering block followed by a detection block at varying mixing times to map the exchange rate. Long mixing times enhance the sensitivity to exchange, but they pose challenges for imaging applications that require a stimulated echo sequence with crusher gradients. Thin imaging slices require strong crushers, which can introduce significant diffusion weighting and bias exchange rate estimates. Here, we treat the crushers as an additional encoding block and consider FEXI as a triple diffusion‐encoding sequence. This allows the bias to be corrected in the case of multi‐Gaussian diffusion, but not easily in the presence of restricted diffusion. Our approach addresses challenges in the presence of restricted diffusion and relies on the ability to independently gauge sensitivities to exchange and restricted diffusion for arbitrary gradient waveforms. It follows two principles: (i) the effects of crushers are included in the forward model using signal cumulant expansion; and (ii) timing parameters of diffusion gradients in filter and detection blocks are adjusted to maintain the same level of restriction encoding regardless of the mixing time. This results in the tuned exchange imaging (TEXI) protocol. The accuracy of exchange mapping with TEXI was assessed through Monte Carlo simulations in spheres of identical sizes and gamma‐distributed sizes, and in parallel hexagonally packed cylinders. The simulations demonstrate that TEXI provides consistent exchange rates regardless of slice thickness and restriction size, even with strong crushers. However, the accuracy depends on b‐values, mixing times, and restriction geometry. The constraints and limitations of TEXI are discussed, including suggestions for protocol adaptations. Further studies are needed to optimize the precision of TEXI and assess the approach experimentally in realistic, heterogeneous substrates. [ABSTRACT FROM AUTHOR]

Diffusion‐tensor (DT)‐MRI tractography provides information about properties relevant to muscle health and function, including estimates of architectural properties such as fascicle length, pennation angle, and curvature and diffusion properties such as mean diffusivity (MD) and fractional anisotropy (FA). Tractography settings, including integration algorithms, thresholds for early tract termination, and tract smoothing approaches, impact the accuracy of the muscle property estimates. However, muscle DT‐MRI tractography is performed using a variety of these settings, complicating comparisons between different studies. The effects of different tractography settings on muscle architecture estimates have not been fully explored, and optimized settings for muscle tractography have not yet been determined. We examined the influence of integration algorithm and termination check settings combined with a range of step sizes, termination criteria, and smoothing polynomial orders on tract characteristics, completion/reason for termination, and goodness of fit between fiber tracts and smoothing polynomials using 3‐T DT‐MR images of the lower leg muscles of seven healthy adults. We found that tract length and completion were highly sensitive to strict FA and intersegment angle thresholds (25%–69% reduction in complete fiber tracts from lowest to highest minimum FA threshold and 11%–36% reduction from highest to lowest intersegment angle threshold). Higher order polynomials (third and fourth order vs. second order) better fit the muscle fiber trajectories, but curvature estimates were highly sensitive to smoothing polynomial order (3.9–6.6 m−1 increase for second‐ vs. fourth‐order fitting polynomials). Step size impacted curvature estimates, albeit to a lesser degree. Integration algorithm had little impact, and mean pennation angle, and tract‐based FA and MD, were relatively insensitive to all parameters. The results demonstrate which muscle diffusion measures and architectural estimates are most sensitive to varying tractography settings and support the need for consistent reporting of tractography details to aid interpretation and comparison of results between studies. [ABSTRACT FROM AUTHOR]

Early tumor response prediction can help avoid overtreatment with unnecessary chemotherapy sessions. It is important to determine whether multiple apparent diffusion coefficient indices (S index, ADC‐diff) are effective in the early prediction of pathological response to neoadjuvant chemotherapy (NAC) in breast cancer (BC). Patients with stage II and III BCs who underwent T1WI, diffusion‐weighted imaging (DWI), and dynamic contrast‐enhanced MRI using a 3 T system were included. They were divided into two groups: major histological responders (MHRs, Miller–Payne G4/5) and nonmajor histological responders (nMHRs, Miller–Payne G1–3). Three b values were used for DWI to derive the S index; ADC‐diff values were obtained using b = 0 and 1000 s/mm2. The different interquartile ranges of percentile S‐index and ADC‐diff values after treatment were calculated and compared. The assessment was performed at baseline and after two and four NAC cycles. A total of 59 patients were evaluated. There are some correlations of interquartile ranges of S‐index parameters and ADC‐diff values with histopathological prognostic factors (such as estrogen receptor and human epidermal growth factor receptor 2 expression, all p < 0.05), but no significant differences were found in some other interquartile ranges of S‐index parameters or ADC‐diff values between progesterone receptor positive and negative or for Ki‐67 tumors (all P > 0.05). No differences were found in the dynamic contrast‐enhanced MRI characteristics between the two groups. HER‐2 expression and kurtosis of the S‐index distribution were screened out as independent risk factors for predicting MHR group (p < 0.05, area under the curve (AUC) = 0.811) before NAC. After early NAC (two cycles), only the 10th percentile S index was statistically significant between the two groups (p < 0.05, AUC = 0.714). No significant differences were found in ADC‐diff value at any time point of NAC between the two groups (P > 0.1). These findings demonstrate that the S‐index value may be used as an early predictor of pathological response to NAC in BC; the value of ADC‐diff as an imaging biomarker of NAC needs to be further confirmed by ongoing multicenter prospective trials. [ABSTRACT FROM AUTHOR]

Purpose: To fully characterize the orientation dependence of magnetization transfer (MT) and inhomogeneous MT (ihMT) measures in the whole white matter (WM), for both single‐fiber and crossing‐fiber voxels. Methods: A characterization method was developed using the fiber orientation obtained from diffusion MRI (dMRI) with diffusion tensor imaging (DTI) and constrained spherical deconvolution. This allowed for characterization of the orientation dependence of measures in all of WM, regardless of the number of fiber orientation in a voxel. Furthermore, the orientation dependence inside 31 different WM bundles was characterized to evaluate the homogeneity of the effect. Variation of the results within and between‐subject was assessed from a 12‐subject dataset. Results: Previous results for single‐fiber voxels were reproduced and a novel characterization was produced in voxels of crossing fibers, which seems to follow trends consistent with single‐fiber results. Heterogeneity of the orientation dependence across bundles was observed, but homogeneity within similar bundles was also highlighted. Differences in behavior between MT and ihMT measures, as well as the ratio and saturation versions of these, were noted. Conclusion: Orientation dependence characterization was proven possible over the entirety of WM. The vast range of effects and subtleties of the orientation dependence on MT measures showed the need for, but also the challenges of, a correction method. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to develop a model‐based deep learning architecture to accurately reconstruct fiber orientation distributions (FODs) from a reduced number of diffusion‐weighted images (DWIs), facilitating accurate analysis with reduced acquisition times. Methods: Our proposed architecture, Spherical Deconvolution Network (SDNet), performed FOD reconstruction by mapping 30 DWIs to fully sampled FODs, which have been fit to 288 DWIs. SDNet included DWI‐consistency blocks within the network architecture, and a fixel‐classification penalty within the loss function. SDNet was trained on a subset of the Human Connectome Project, and its performance compared with FOD‐Net, and multishell multitissue constrained spherical deconvolution. Results: SDNet achieved the strongest results with respect to angular correlation coefficient and sum of squared errors. When the impact of the fixel‐classification penalty was increased, we observed an improvement in performance metrics reliant on segmenting the FODs into the correct number of fixels. Conclusion: Inclusion of DWI‐consistency blocks improved reconstruction performance, and the fixel‐classification penalty term offered increased control over the angular separation of fixels in the reconstructed FODs. [ABSTRACT FROM AUTHOR]

Purpose: Demonstrating and assessing self‐supervised machine‐learning fitting of the VERDICT (vascular, extracellular and restricted diffusion for cytometry in tumors) model for prostate cancer. Methods: We derive a self‐supervised neural network for fitting VERDICT (ssVERDICT) that estimates parameter maps without training data. We compare the performance of ssVERDICT to two established baseline methods for fitting diffusion MRI models: conventional nonlinear least squares and supervised deep learning. We do this quantitatively on simulated data by comparing the Pearson's correlation coefficient, mean‐squared error, bias, and variance with respect to the simulated ground truth. We also calculate in vivo parameter maps on a cohort of 20 prostate cancer patients and compare the methods' performance in discriminating benign from cancerous tissue via Wilcoxon's signed‐rank test. Results: In simulations, ssVERDICT outperforms the baseline methods (nonlinear least squares and supervised deep learning) in estimating all the parameters from the VERDICT prostate model in terms of Pearson's correlation coefficient, bias, and mean‐squared error. In vivo, ssVERDICT shows stronger lesion conspicuity across all parameter maps, and improves discrimination between benign and cancerous tissue over the baseline methods. Conclusion: ssVERDICT significantly outperforms state‐of‐the‐art methods for VERDICT model fitting and shows, for the first time, fitting of a detailed multicompartment biophysical diffusion MRI model with machine learning without the requirement of explicit training labels. [ABSTRACT FROM AUTHOR]

Diffusion-weighted magnetic resonance imaging (DW-MRI) performed before target temperature management, within 6 h of return of spontaneous circulation (ROSC), is defined as ultra-early DW-MRI. In previous studies, high-signal intensity (HSI) on ultra-early DW-MRI can predict poor neurological outcomes (Cerebral Performance Category 3–5 at 6-months post-ROSC). We aimed to assess the optimal-timing for ultra-early DW-MRI to avoid false-negative outcomes post out-of-hospital cardiac arrest, considering cardiopulmonary resuscitation (CPR) factors. The primary outcomes were HSI in the cerebral cortex or deep gray matter on ultra-early DW-MRI. The impact of CPR factors and ROSC to DW-MRI scan-interval on HSI-presence was assessed. Of 206 included patients, 108 exhibited HSI-presence, exclusively associated with poor neurological outcomes. In multivariate regression analysis, ROSC to DW-MRI scan-interval (adjusted odds ratio [aOR], 1.509; 95% confidence interval (CI): 1.113–2.046; P = 0.008), low-flow time (aOR, 1.176; 95%CI: 1.121–1.233; P < 0.001), and non-shockable rhythm (aOR, 9.974; 95%CI: 3.363–29.578; P < 0.001) were independently associated with HSI-presence. ROSC to DW-MRI scan-interval cutoff of ≥ 2.2 h was particularly significant in low-flow time ≤ 21 min or shockable rhythm group. In conclusion, short low-flow time and shockable rhythm require a longer ROSC to DW-MRI scan-interval. Prolonged low-flow time and non-shockable rhythm reduce the need to consider scan-interval. [ABSTRACT FROM AUTHOR]

Background: CLCN2-related leukoencephalopathy (CC2L) is a rare autosomal recessive disorder caused by biallelic variants of CLCN2, which encodes chloride channel 2. Although CC2L is associated with distinct radiological features, it presents with a wide range of clinical features. Case presentation: A 34-year-old woman presented to our hospital with a sudden onset of vertigo with headache. The patient reported intermittent headaches and tingling in both arms since the age of 31 years. On the first visit, the patient was alert and neurologically intact, except for slight hyperreflexia of the limbs without laterality. Head magnetic resonance imaging (MRI) showed high-intensity signals on axial T2-weighted fluid-attenuated inversion recovery and diffusion-weighted images bilaterally in the posterior limbs of the internal capsules, cerebral peduncles, superior and middle cerebellar peduncles, decussation of superior cerebellar peduncles, and central tegmental tract. All the patient's symptoms were resolved or eased following supportive care. The patient stopped attending our hospital at the age of 46 years. At 51 years of age, the patient revisited our hospital because of the recurrence of vertigo, headache, and nausea. She did not present with any abnormalities by neurological examination. Head MRI showed widespread high-intensity signals similar to those 17 years ago. Genetic testing revealed compound heterozygous variants in CLCN2 (NM_004366.6): a novel variant c.1828 C > T, p.(Arg 610*) from her father and c.61dup, p.(Leu21Profs*27) from her mother. The patient was finally diagnosed with CC2L. She received supportive treatment, which made her symptoms manageable. Conclusions: This is a detailed report of a patient with adult-onset CC2L who was successfully diagnosed and followed up with head MRI. This report provides new insights into CC2L and highlights its persistent, distinct, and stable characteristics observed in head MRI over one decade and the difficulty in forming a diagnosis without MRI when patients have minimal and common symptoms, such as in the present case. [ABSTRACT FROM AUTHOR]

Objective: We sought to evaluate the use of quantitative Dixon (Q-Dixon) and intravoxel incoherent motion diffusion imaging (IVIM) for the differential diagnosis of aplastic anemia (AA) and acute myeloid leukemia (AML). Methods: Between August 2021 and October 2023, we enrolled 68 diagnosed patients, including 36 patients with AA and 32 patients with AML, as well as 26 normal controls. All patients underwent 3-Tesla magnetic resonance imaging, which included IVIM and T2*-corrected Q-Dixon imaging at the L2-4 level. The iliac crest biopsy's pathology was used as the diagnostic criterion. The interobserver measurement repeatability was evaluated using the intraclass correlation coefficient (ICC). One-way analysis of variance, Spearman analysis, and receiver operating characteristic curve analysis were used. Results: The fat fraction (FF) and perfusion fraction (f) values were statistically significantly different between the three groups (p < 0.001 and p = 0.007). The FF and f values in the AA group were higher than those in the AML group. The true apparent diffusion coefficient (D) value was substantially negatively correlated to the FF and R2* values (r = -0.601, p < 0.001; r = -0.336, p = 0.002). The f value was positively correlated with both FF and pseudo-apparent diffusion coefficient (D*) values (r = 0.376, p < 0.001; r = 0.263, p = 0.017) and negatively correlated with the D value (r = -0.320, p = 0.003). The FF and f values were negatively correlated with the degree of myelodysplasia (r = -0.597, p < 0.001; r = -0.454, p = 0.004), and the D value was positively correlated with the degree of myelodysplasia (r = 0.395, p = 0.001). For the differential diagnosis of AA and AML, the Q-Dixon model's sensitivity (93.75%) and specificity (84%) confirmed that it outperformed the IVIM model. Conclusion: Q-Dixon parameters have the potential to be used as new biomarkers to differentiate AA from AML. [ABSTRACT FROM AUTHOR]

Diffusion-weighted magnetic resonance imaging (DMRI) is a potential tool to assess changes in brain connectivity and microstructure resulting from physical and occupational therapy in young children with cerebral palsy. This works was carried out to assess whether DMRI can detect changes after 36 weeks of physical and occupational therapy in the microstructure and connectivity of the brains of children with cerebral palsy and determine whether imaging findings correlate with changes in clinical measures of motor function. Five children underwent anatomical MRI and DMRI and evaluations of motor function skills at baseline and after 36 weeks of intensive or once-weekly physical and occupational Perception-Action Approach therapies. Diffusion tensor imaging and constrained spherical deconvolution methods were used to calculate fractional anisotropy (FA) and fiber orientation distribution functions (fODFs), respectively. The fODFs were used to generate tractograms of the cerebrospinal tract (CST). After 36 weeks of physical and occupational therapy, all children showed increases in motor function. No changes were observed in anatomical MRI before and after therapy but CST tractography did show small differences indicating possible altered microstructure and connectivity in the brain. FA values along the CSTs, however, showed no significant changes. Reliable longitudinal DMRI can be employed in toddler-aged children with CP and DMRI has the potential to monitor neuroplastic changes in white matter microstructure. However, there is a high variability between subjects and clinical improvements were not always correlated with measures of FA along the CST. [ABSTRACT FROM AUTHOR]

Introduction: The primary objective was to investigate the value of the fluid attenuated inversion recovery (FLAIR) signal intensity ratio (SIR) in identifying stroke within 4.5 h. The secondary objective was to ascertain whether large vessel occlusion (LVO) mediated the relationship between the SIR and stroke within 4.5 h. Methods: We analyzed 633 acute stroke patients within 24 h of clear symptom onset. The SIR and DWI-FLAIR mismatch were evaluated. First, we determined whether demographic variables, vascular risk factors and LVO were related to stroke within 4.5 h with multivariate logistic regression analyses and stratified regression analysis. Next, we used mediation analysis to determine whether LVO explained the association between SIR and stroke within 4.5 h. Finally, we used receiver operating characteristic (ROC) analysis to assess the value of SIR, independent variable, and multiparameter models in identifying stroke within 4.5 h and compared with DWI-FLAIR mismatch. Results: Hyperlipemia, LVO and SIR were associated with stroke within 4.5 h. Mediation analysis revealed that LVO partially mediated the relationship between SIR and stroke within 4.5 h (p < 0.001). The multiparameter model (hyperlipemia, LVO and SIR) showed significantly improved performance (AUC 0.869) in identifying stroke within 4.5 h over DWI-FLAIR mismatch (0.684), hyperlipemia (0.632), LVO (0.667) and SIR (0.773) models. Conclusion: SIR is associated with stroke within 4.5 h, and LVO partially mediates this relationship. A multiparameter model combining hyperlipemia, LVO and SIR can more accurately identify stroke within 4.5 h than individual parameter models. [ABSTRACT FROM AUTHOR]

Diffusion-weighted imaging (DWI) is a magnetic resonance imaging (MRI) technique that provides information about the Brownian motion of water molecules within biological tissues. DWI plays a crucial role in stroke imaging and oncology, but its diagnostic value can be compromised by the inherently low signal-to-noise ratio (SNR). Conventional supervised deep learning-based denoising techniques encounter challenges in this domain as they necessitate noise-free target images for training. This work presents a novel approach for denoising and evaluating DWI scans in a self-supervised manner, eliminating the need for ground-truth data. By leveraging an adapted version of Stein's unbiased risk estimator (SURE) and exploiting a phase-corrected combination of repeated acquisitions, we outperform both state-of-the-art self-supervised denoising methods and conventional non-learning-based approaches. Additionally, we demonstrate the applicability of our proposed approach in accelerating DWI scans by acquiring fewer image repetitions. To evaluate denoising performance, we introduce a self-supervised methodology that relies on analyzing the characteristics of the residual signal removed by the denoising approaches. [ABSTRACT FROM AUTHOR]

We determined the intersubject association between the rhythmic entrainment abilities of human subjects during a synchronization-continuation tapping task (SCT) and the macro- and microstructural properties of their superficial (SWM) and deep (DWM) white matter. Diffusion-weighted images were obtained from 32 subjects who performed the SCT with auditory or visual metronomes and five tempos ranging from 550 to 950 ms. We developed a method to determine the density of short-range fibers that run underneath the cortical mantle, interconnecting nearby cortical regions (U-fibers). Notably, individual differences in the density of U-fibers in the right audiomotor system were correlated with the degree of phase accuracy between the stimuli and taps across subjects. These correlations were specific to the synchronization epoch with auditory metronomes and tempos around 1.5 Hz. In addition, a significant association was found between phase accuracy and the density and bundle diameter of the corpus callosum (CC), forming an interval-selective map where short and long intervals were behaviorally correlated with the anterior and posterior portions of the CC. These findings suggest that the structural properties of the SWM and DWM in the audiomotor system support the tapping synchronization abilities of subjects, as cortical U-fiber density is linked to the preferred tapping tempo and the bundle properties of the CC define an interval-selective topography. [ABSTRACT FROM AUTHOR]

Contrast-enhanced breast magnetic resonance imaging (MRI) is currently recommended as a screening tool for high-risk women and has been advocated for women with radiologically dense breast tissue. While breast MRI is acknowledged for its high sensitivity (with an exception for lower-grade ductal carcinoma in situ (DCIS) where emerging techniques like diffusion-weighted imaging offer improvement), its limitations include sensitivity to hormonal changes and a relatively high false-positive rate, potentially leading to overdiagnosis, increased imaging uncertainty, and unnecessary biopsies. These factors can exacerbate patient anxiety and impose additional costs. Molecular imaging with breast-targeted Positron Emission Tomography (PET) has shown the capability to detect malignancy independent of breast density and hormonal changes. Furthermore, breast-targeted PET has shown higher specificity when compared with MRI. However, traditional PET technology is associated with high radiation dose, which can limit its widespread use particularly in repeated studies or for undiagnosed patients. In this case report, we present a clinical application of low-dose breast imaging utilizing a breast-targeted PET camera (Radialis PET imager, Radialis Inc). The case involves a 33-year-old female patient who had multiple enhanced lesions detected on breast MRI after surgical removal of a malignant phyllodes tumor from the right breast. A benign core biopsy was obtained from the largest lesion seen in the left breast. One month after the MRI, 18F-fluorodeoxyglucose (18F-FDG) PET imaging session was performed using the Radialis PET Imager. Although the Radialis PET Imager has proven high count sensitivity and the capability to detect breast lesions with low metabolic activity (at a dose similar to mammography), no areas of increased 18F-FDG uptake were visualized in this particular case. The patient underwent a right-sided nipplesparing mastectomy and left-sided lumpectomy, with bilateral reconstruction. [ABSTRACT FROM AUTHOR]

Diffusion-weighted imaging (DWI) is a technique used to probe the random microscopic motion of water protons in living tissue, represented by a parameter measurement of apparent diffusion coefficient (ADC) values. This study aimed to measure the ADC values of various fetal organs and placenta using 3T at various gestational ages. This was a prospective observational study. A total of 103 singleton pregnancies from 20 to 38 weeks of gestational age were included. Diffusion-weighted imaging was performed in the axial plane from the fetal head to the trunk with the following parameters: TR: 2000–2500 ms; TE: 88 ms; FOV: 250 mm; 256 matrix; slice thickness: 4 mm with a 0 mm gap; acquisition time: 1 min, 18 s. Diffusion gradient values were b = 0 and b = 700 s/mm2. ADC was measured in fetal brain regions (frontal white matter, occipital white matter, centrum semiovale, pons, thalamus, cerebellum, and fetal organs (lungs, kidney, and placenta). ANOVA was used to calculate the mean ADC values. Karl Pearson's coefficient of correlation was used to evaluate the correlation between ADC values and increasing gestational age. The mean ADC values of brain regions were: frontal white matter (1.64 ± 0.08 × 10− 3 mm2 /s, F-39.10,p-<0.001), occipital white matter (1.64 ± 0.06 × 10− 3 mm2/s, F-26.14, p-<0.001), centrum semiovale (1.62 ± 0.03 × 10− 3 mm2/s, F-49.88,p-<0.001, pons (1.23 ± 0.09 × 10− 3 mm2/s F-9.14,p-<0.001)), Thalamus (1.21 ± 0.07 × 10− 3 mm2/s, F-13.54,p-<0.001) and cerebellum (1.36 ± 0.10 × 10− 3 mm2 /s, F-4.19,p-<0.001). The mean ADC values of fetal organs were lung (1.92 ± 0.15 × 10− 3 mm2 /s, F-28.24, p-<0.001), kidney (1.34 ± 0.11 × 10− 3 mm2 /s, F-1.05, p- 0.37) and placenta (1.94 ± 0.11 × 10− 3 mm2 /s, F-160.33, p-<0.001). White-matter regions showed a significant positive correlation with increasing gestational age. Statistically, a negative correlation was observed between increasing gestational age and ADC measurements obtained in the thalamus, cerebellum, pons, and kidney. This will be one of the first few studies to provide the ADC values of the fetal brain and fetal organs using 3T MRI. The current study shows that diffusion-weighted MRI can offer a promising technique to evaluate the structural development of fetal organs and can potentially lead to a biomarker for predicting the functionality of the fetal organs in abnormalities. [ABSTRACT FROM AUTHOR]

Background: Musculoskeletal alterations causing reduced range of motion of the ankle joint are common in children with cerebral palsy (CP). Objective measurements of passive joint resistance and three-dimensional skeletal muscle volume and muscle architecture can lead to a comprehensive understanding of which factors influence joint range of motion. Research question: To investigate the relation between the passive dorsiflexion of the ankle joint, biomechanical contributing factors to the passive joint resistance, and muscular architectural properties of the triceps surae muscle in children with CP. Methods: In this cross-sectional observational study, 14 children with spastic CP (bilateral: 5, unilateral: 9, Gross Motor Function Classification System (GMFCS) level I:11, II:3) naïve to intramuscular tone reducing treatment, and 14 TD children were included. The passive dorsiflexion of the ankle was measured with a goniometer. Passive joint resistance and related parameters were estimated based on a biomechanical model and measurements using a motorized device, the Neuroflexor. Three-dimensional muscle architecture was quantified with diffusion tensor magnetic resonance imaging (DT-MRI). Results: In the CP group, the median [min, max] passive dorsiflexion was decreased in the most affected leg (MAL) compared to the less affected leg (LAL) (2.5° [-25°, 20°] vs. 12.5° [5°, 30°], p = 0.001). The stiffness coefficient (Nm/rad) in the MAL was significantly higher in children with CP compared to TD children (7.10 [3.39, 62.00] vs. 2.82 [1.24, 10.46], p = 0.015). Muscle architecture properties did not differ between CP and TD, except for pennation angle in the medial gastrocnemius (MG) of the MAL (CP 17.64° (2.29) vs. TD 21.46° (3.20), p = 0.017). The stiffness coefficient, in the MAL, correlated negatively to passive dorsiflexion (rs=-0.638) and pennation angle in medial gastrocnemius (rs=-0.964), and the non-linear coefficient (Non-linear 1) correlated negatively to the fascicle length of the medial gastrocnemius (rs=-0.857). Conclusion: This study shows that stiffness of the plantarflexors is related to decreased passive dorsiflexion of the ankle and muscle structure of the MG in high-functioning children with spastic CP. Assessments of how dynamic components as well as microscopic muscle alterations contribute to joint stiffness in the plantarflexors in individuals with CP are warranted. Trial registration: Retrospectively registered in ClinicalTrials.gov, NCT05447299. Observational study. Study start: 2019-01-15, register date: 2022-07-01. [ABSTRACT FROM AUTHOR]

Background Purpose Methods Results Conclusions Quantitative imaging biomarkers (QIBs) can characterize tumor heterogeneity and provide information for biological guidance in radiotherapy (RT). Time‐dependent diffusion MRI (TDD‐MRI) derived parameters are promising QIBs, as they describe tissue microstructure with more specificity than traditional diffusion‐weighted MRI (DW‐MRI). Specifically, TDD‐MRI can provide information about both restricted diffusion and diffusional exchange, which are the two time‐dependent effects affecting diffusion in tissue, and relevant in tumors. However, exhaustive modeling of both effects can require long acquisitions and complex model fitting. Furthermore, several introduced TDD‐MRI measurements can require high gradient strengths and/or complex gradient waveforms that are possibly not available in RT settings.In this study, we investigated the feasibility of a simple analysis framework for the detection of restricted diffusion and diffusional exchange effects in the TDD‐MRI signal. To promote the clinical applicability, we use standard gradient waveforms on a conventional 1.5 T MRI system with moderate gradient strength (Gmax = 45 mT/m), and on a hybrid 1.5 T MRI‐Linac system with low gradient strength (Gmax = 15 mT/m).Restricted diffusion and diffusional exchange were simulated in geometries mimicking tumor microstructure to investigate the DW‐MRI signal behavior and to determine optimal experimental parameters. TDD‐MRI was implemented using pulsed field gradient spin echo with the optimized parameters on a conventional MRI system and a MRI‐Linac. Experiments in green asparagus and 10 patients with brain lesions were performed to evaluate the time‐dependent diffusion (TDD) contrast in the source DW‐images.Simulations demonstrated how the TDD contrast was able to differentiate only dominating diffusional exchange in smaller cells from dominating restricted diffusion in larger cells. The maximal TDD contrast in simulations with typical cancer cell sizes and in asparagus measurements exceeded 5% on the conventional MRI but remained below 5% on the MRI‐Linac. In particular, the simulated TDD contrast in typical cancer cell sizes (r = 5–10 µm) remained below or around 2% with the MRI‐Linac gradient strength. In patients measured with the conventional MRI, we found sub‐regions reflecting either dominating restricted diffusion or dominating diffusional exchange in and around brain lesions compared to the noisy appearing white matter.On the conventional MRI system, the TDD contrast maps showed consistent tumor sub‐regions indicating different dominating TDD effects, potentially providing information on the spatial tumor heterogeneity. On the MRI‐Linac, the available TDD contrast measured in asparagus showed the same trends as with the conventional MRI but remained close to typical measurement noise levels when simulated in common cancer cell sizes. On conventional MRI systems with moderate gradient strengths, the TDD contrast could potentially be used as a tool to identify which time‐dependent effects to include when choosing a biophysical model for more specific tumor characterization. [ABSTRACT FROM AUTHOR]

White matter microvascular alterations in temporal lobe epilepsy (TLE) may be relevant to acquired neurodegenerative processes and cognitive impairments associated with this condition. We quantified microvascular changes, myelin, axonal, glial and extracellular-matrix labelling in the gyral core and deep temporal lobe white matter regions in surgical resections from 44 TLE patients with or without hippocampal sclerosis. We compared this pathology data with in vivo pre-operative MRI diffusion measurements in co-registered regions and neuropsychological measures of cognitive impairment and decline. In resections, increased arteriolosclerosis was observed in TLE compared to non-epilepsy controls (greater sclerotic index, p < 0.001), independent of age. Microvascular changes included increased vascular densities in some regions but uniformly reduced mean vascular size (quantified with collagen-4, p < 0.05–0.0001), and increased pericyte coverage of small vessels and capillaries particularly in deep white matter (quantified with platelet-derived growth factor receptorβ and smooth muscle actin, p < 0.01) which was more marked the longer the duration of epilepsy (p < 0.05). We noted increased glial numbers (Olig2, Iba1) but reduced myelin (MAG, PLP) in TLE compared to controls, particularly prominent in deep white matter. Gene expression analysis showed a greater reduction of myelination genes in HS than non-HS cases and with age and correlation with diffusion MRI alterations. Glial densities and vascular size were increased with increased MRI diffusivity and vascular density with white matter abnormality quantified using fixel-based analysis. Increased perivascular space was associated with reduced fractional anisotropy as well as age-accelerated cognitive decline prior to surgery (p < 0.05). In summary, likely acquired microangiopathic changes in TLE, including vascular sclerosis, increased pericyte coverage and reduced small vessel size, may indicate a functional alteration in contractility of small vessels and haemodynamics that could impact on tissue perfusion. These morphological features correlate with white matter diffusion MRI alterations and might explain cognitive decline in TLE. [ABSTRACT FROM AUTHOR]

Background: Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder associated with alterations in structural and functional coupling in gray matter. However, despite the detectability and modulation of brain signals in white matter, the structure-function coupling in white matter in autism remains less explored. Methods: In this study, we investigated structural-functional coupling in white matter (WM) regions, by integrating diffusion tensor data that contain fiber orientation information from WM tracts, with functional connectivity tensor data that reflect local functional anisotropy information. Using functional and diffusion magnetic resonance images, we analyzed a cohort of 89 ASD and 63 typically developing (TD) individuals from the Autism Brain Imaging Data Exchange II (ABIDE-II). Subsequently, the associations between structural-functional coupling in WM regions and ASD severity symptoms assessed by Autism Diagnostic Observation Schedule-2 were examined via supervised machine learning in an independent test cohort of 29 ASD individuals. Furthermore, we also compared the performance of multi-model features (i.e. structural-functional coupling) with single-model features (i.e. functional or structural models alone). Results: In the discovery cohort (ABIDE-II), individuals with ASD exhibited widespread reductions in structural-functional coupling in WM regions compared to TD individuals, particularly in commissural tracts (e.g. corpus callosum), association tracts (sagittal stratum), and projection tracts (e.g. internal capsule). Notably, supervised machine learning analysis in the independent test cohort revealed a significant correlation between these alterations in structural-functional coupling and ASD severity scores. Furthermore, compared to single-model features, the integration of multi-model features (i.e., structural-functional coupling) performed best in predicting ASD severity scores. Conclusion: This work provides novel evidence for atypical structural-functional coupling in ASD in white matter regions, further refining our understanding of the critical role of WM networks in the pathophysiology of ASD. [ABSTRACT FROM AUTHOR]

Our case demonstrated unique cytomegalovirus (CMV) encephalitis posthaploidentical donor hematopoietic stem cell transplantation (HID-HSCT), with early findings on diffusion-weighted brain magnetic resonance imaging (MRI) in the absence of any neurologic symptoms. A 54-year-old Chinese man with acute lymphoblastic leukemia (Philadelphia chromosome-negative) underwent HIDHSCT. After HSCT, the patient developed CMV viremia and severe acute graftversus- host disease. Recurrence of CMV viremia was observed. On day 129, brain MRI was performed to determine the cause for the intermittent fever. Diffusionweighted imaging (DWI) revealed several bright spots in the cortex of the frontal lobes and anterior angle of the left lateral ventricle. Subsequently, he developed transplant-associated thrombotic microangiopathy, posterior reversible encephalopathy syndrome, and enlargement of lesions alongside the ventricular wall on a brain MRI series. Metagenomic next-generation sequencing (NGS) of the cerebrospinal fluid (CSF) led to the final diagnosis of CMV encephalitis. Although ganciclovir combined with foscarnet was administered, the patient's consciousness deteriorated, followed by respiratory failure. The patient died on day 198. Additionally, we performed a systematic review to comprehensively analyze this disease. Regarding treatment, immunological therapies, including virus-specific T cells from a third donor and CMV-cytotoxic T lymphocytes, may be more effective. This case report and systematic review underscores the complexities of managing CMV ventriculoencephalitis in HSCT recipients and emphasizes the importance of early diagnosis by brain MRI and CSF polymerase chain reaction or NGS and ongoing research in improving outcomes. [ABSTRACT FROM AUTHOR]

Objectives: Neuroimaging studies of dyskinetic cerebral palsy (CP) are scarce and the neuropathological underpinnings are not fully understood. We delineated the corticospinal tract (CST) and cortico‐striatal‐thalamocortical (CSTC) pathways with probabilistic tractography to assess their (1) integrity and (2) association with motor functioning in people with dyskinetic CP. Methods: Diffusion weighted magnetic resonance images were obtained for 33 individuals with dyskinetic CP and 33 controls. Fractional anisotropy (FA) and mean diffusivity (MD) for the CST and the CSTC pathways were compared between groups. Correlation analyses were performed between tensor metric values and motor function scores of participants with dyskinetic CP as assessed by the Gross Motor Function Classification System (GMFCS), the Bimanual Fine Motor Function (BFMF), and the Manual Ability Classification System (MACS). Results: White matter integrity in both the CST and the CSTC pathways was reduced in people with dyskinetic CP. The GMFCS, MACS and, less commonly, the BFMF were associated with FA and, particularly, MD in most portions of these pathways. Interpretation: The present study advances our understanding of the involvement of white matter microstructure in sensorimotor pathways and its relationship with motor impairment in people with dyskinetic CP. Our results are consistent with well‐described relationships between upper limb function and white matter integrity in the CST and CSTC pathways in other forms of CP. This knowledge may ultimately help prognosis and therapeutic programmes. [ABSTRACT FROM AUTHOR]

Background: the aim of this study is to assess the performance of diffusion-weighted imaging (DWI) and apparent diffusion coefficient (ADC) values in predicting the response to neoadjuvant chemoradiation therapy (CRT) and outcome in patients with locally advanced rectal cancer (LARC). Materials and Methods: ninety-four patients with magnetic resonance imaging (MRI) pre- and post-neoadjuvant treatment were retrospectively enrolled. Three regions of interest (ROIs) were manually drawn on three different slices of the tumor for every DWI sequence. ROIs were positioned to include only high signal areas and avoid artifacts or necrotic areas. ROIs were automatically copied onto the corresponding ADC maps and the system derived three different ADC values, distinguishing between mean, maximum, and minimum values, and the standard deviation (SD). Only mean ADC values were considered. After surgical intervention, pTNM and the Mandard tumor regression grade (TRG) were obtained. Patients with a TRG of 1–2 were classified as responders, while patients with a TRG from 3 to 5 were classified as non-responders. Results: no correlation was found between pre-ADC values and TRG classes, while post-ADC and ΔADC values showed a significant correlation with TRG classes (r = −0.285, p = 0.002 and r = −0.290, p = 0.019, respectively). Post-ADC values were statistically different between responders and non-responders (p = 0.019). When considering the relation between overall survival (OS) and ADC values, pre-ADC showed a negative correlation with OS (r = −0.381, p = 0.001), while a positive correlation was found between ΔADC values and OS (r = 0.323, p = 0.013). According to ΔADC values, the mean OS time between responders and non-responders showed a significant difference (p = 0.030). A statistical difference was found between TRG classes and OS (p = 0.038) and by dividing patients in responders and non-responders (p = 0.019). Conclusions: the pre-ADC and ΔADC values could be used as useful predictors for patient prognosis, thus helping the treatment planning. On the other hand, the post-ADC values, thanks to their relationship with the TRG classes, could be the ideal tool to predict the histopathological response and plan a conservative approach to the treatment of rectal cancer. [ABSTRACT FROM AUTHOR]

Background/Objectives: Small-vessel occlusion, previously referred to as lacunar infarcts, accounts for approximately one-third of all ischemic strokes, using an axial diameter of less than 20 mm on diffusion-weighted imaging. However, this threshold may not adequately differentiate small-vessel occlusion from other pathologies, such as branch atheromatous disease (BAD) and embolism. This study aimed to assess the clinical significance and pathological implications of acute small subcortical infarctions (SSIs) based on infarct diameter. Methods: We conducted a retrospective case–control study using data from stroke patients recorded between 2016 and 2021 of the Stroke Registry in Chang Gung Healthcare System. Patients with acute SSIs in penetrating artery territories were included. Key variables such as patient demographics, stroke severity, and medical history were collected. Infarcts were categorized based on size, and the presence of early neurological deterioration (END) and favorable functional outcomes were assessed. Results: Among the 855 patients with acute SSIs, the median age was 70 years and the median National Institutes of Health Stroke Scale (NIHSS) score at arrival was four. END occurred in 97 patients (11.3%). Those who experienced END were significantly less likely to achieve a favorable functional outcome compared to those who did not (18.6% vs. 59.9%, p < 0.001). The incidence of END increased progressively with infarct sizes of 15 mm or larger, with the optimal threshold for predicting END identified as 15.5 mm and for BAD, it was 12.1 mm. A multiple logistic regression analysis revealed that motor tract involvement [adjusted odds ratio (aOR) 2.3; 95% confidence interval (CI) 1.1–4.7], an initial heart rate greater than 90 beats per minute (aOR 2.3; 95% CI 1.2–4.3), and a larger infarct size (15 mm to less than 20 mm vs. 10 mm to less than 15 mm; aOR 3.0; 95% CI 1.4–6.3) were significantly associated with END. Conclusions: Our findings suggest that setting the upper limit for small-vessel occlusion at 15 mm would be more effective in distinguishing it from BAD. However, these findings should be interpreted in the context of the retrospective design and study population. Further multi-center research utilizing high-resolution vessel wall imaging is necessary to refine this threshold and enhance diagnostic accuracy. [ABSTRACT FROM AUTHOR]

Background/Objectives: The accurate quantification of peripheral nerve axonal regeneration after injury is critically important. Current strategies are limited to detecting early reinnervation. DTI is an MRI modality permitting the assessment of fractional anisotropy, which increases with axonal regeneration. The aim of this pilot study is to evaluate DTI as a potential predictive factor of clinical outcome after median nerve section and microsurgical repair. Methods: We included 10 patients with a complete section of the median nerve, who underwent microsurgical repair up to 7 days after injury. The follow-up period was 1 year, including the current strategy with clinical visits, the Rosén–Lundborg score and electroneuromyography. Additionally, DTI MRI of the injured wrist was planned 1, 3 and 12 months post-operatively and once for the contralateral wrist. Results: The interobserver reliability of DTI measures was almost perfect (ICC 0.802). We report an early statistically significant increase in the fractional anisotropy value after median nerve repair, especially in the region located distal to the suture. Meanwhile, Rosén–Lundborg score gradually increased between the third and sixth month, and continued to increase between the sixth and twelfth month. Conclusions: DTI outcomes three months post-operation could offer greater predictability compared to current strategies. This would enable faster decision-making regarding the need for a potential re-operation in cases of inadequate early reinnervation. [ABSTRACT FROM AUTHOR]

Background: Laparoscopic abdominal surgery is a minimally invasive procedure that requires meticulous preoperative preparation. Advanced methods in Magnetic Resonance Imaging (MRI) provide comprehensive insights, which have the potential to enhance surgical results. The present research assesses the effectiveness of sophisticated MRI techniques in forecasting the outcome of laparoscopic abdominal procedures. Methodology: Prospective research was carried out with 100 patients who were having different laparoscopic abdominal surgeries. Prospective participants were chosen according to predetermined criteria and had preoperative high-resolution MRI, which included functional imaging methods such as diffusion-weighted imaging (DWI). The predictive criteria evaluated were surgical results, duration of surgery, recuperation after surgery, and rates of complications. To assess the precision, sensitivity, and specificity of MRI predictions, statistical studies were performed. Results: Advanced MRI methods demonstrated a high level of accuracy in predicting surgical outcomes in 82% of instances. Surgical procedures with significant complexity had a higher accuracy rate of 90%. A strong correlation was seen between MRI results and intra-operative problems (p < 0.05), successfully predicting difficulties in 24 out of 30 instances. An accuracy rate of 75% was achieved in post-operative recovery forecasts. Achieving 85% sensitivity and 78% specificity, MRI predictions demonstrated high accuracy. Surgeons attested that MRI forecasts were beneficial for pre-operative planning in 88% of instances. Conclusion Advanced MRI methods show outstanding effectiveness in forecasting the results of laparoscopic abdominal procedures. This methodology is very advantageous in intricate scenarios and in predicting difficulties that may arise after surgery. The exceptional prediction precision justifies the use of sophisticated MRI in pre-operative evaluations to enhance surgical planning and patient safety. [ABSTRACT FROM AUTHOR]

The article examines the management of Stage III non‐small cell lung cancer at a regional radiotherapy center in Australia, revealing delays in treatment initiation for many patients. The study emphasizes the need to address these delays to prevent cancer progression and missed opportunities for curative treatment, particularly in rural and regional areas. Additionally, the article discusses the outcomes of patients with oral cavity squamous cell carcinoma who underwent surgery followed by adjuvant radiation therapy, noting a 5-year overall survival rate of 50% and identifying factors associated with poorer outcomes. [Extracted from the article]