Search

Objective. This study presents a universal phantom for positron emission tomography (PET) that allows arbitrary static and dynamic activity distributions of various complexities to be generated using a single PET acquisition.Approach. We collected a high-statistics dataset (with a total of 22.4 × 109prompt coincidences and an event density of 2.75 × 106events mm-3) by raster-scanning a single plane with a22Na point source mounted on a robotic arm in the field-of-view of the uEXPLORER PET/CT scanner. The source position was determined from the reconstructed dynamic frames. Uniquely, true coincidences were separated from scattered and random events based on the distance between their line-of-response and the known source location. Finally, we randomly sampled the dataset to generate the desired activity distributions modeling several different phantoms.Main results. Overall, the target and the reconstructed phantom images had good agreement. The analysis of a simple geometric distribution showed high quantitative accuracy of the phantom, with mean error of

Acute intoxication with cholinesterase inhibiting organophosphates (OP) can produce life-threatening cholinergic crisis and status epilepticus (SE). Survivors often develop long-term neurological consequences, including spontaneous recurrent seizures (SRS) and impaired cognition. Numerous studies implicate OP-induced neuroinflammation as a pathogenic mechanism contributing to these chronic sequelae; however, little is known about the inflammatory phenotype of innate immune cells in the brain following acute OP intoxication. Thus, the aim of this study was to characterize the natural history of microglial and astrocytic inflammatory phenotypes following acute intoxication with the OP, diisopropylfluorophosphate (DFP). Adult male and female Sprague-Dawley rats were administered a single dose of DFP (4 mg/kg, sc) followed by standard medical countermeasures. Within minutes, animals developed benzodiazepine-resistant SE as determined by monitoring seizures using a modified Racine scale. At 1, 3, 7, 14, and 28 d post-exposure (DPE), neuroinflammation was assessed using translocator protein (TSPO) positron emission tomography (PET) and magnetic resonance imaging (MRI). In both sexes, we observed consistently elevated radiotracer uptake across all examined brain regions and time points. A separate group of animals was euthanized at these same time points to collect tissues for immunohistochemical analyses. Colocalization of IBA-1, a marker for microglia, with iNOS or Arg1 was used to identify pro- and anti-inflammatory microglia, respectively; colocalization of GFAP, a marker for astrocytes, with C3 or S100A10, pro- and anti-inflammatory astrocytes, respectively. We observed shifts in the inflammatory profiles of microglia and astrocyte populations during the first month post-intoxication, largely in hyperintense inflammatory lesions in the piriform cortex and amygdala regions. In these areas, iNOS+ proinflammatory microglial cell density peaked at 3 and 7 DPE, while anti-inflammatory Arg1+ microglia cell density peaked at 14 DPE. Pro- and anti-inflammatory astrocytes emerged within 7 DPE, and roughly equal ratios of C3+ pro-inflammatory and S100A10+ anti-inflammatory astrocytes persisted at 28 DPE. In summary, microglia and astrocytes adopted mixed inflammatory phenotypes post-OP intoxication, which evolved over one month post exposure. These activated cell populations were most prominent in the piriform and amygdala areas and were more abundant in males compared to females. The temporal relationship between microglial and astrocytic responses suggests that initial microglial activity may influence delayed, persistent astrocytic responses. Further, our findings identify putative windows for inhibition of OP-induced neuroinflammatory responses in both sexes to evaluate the therapeutic benefit of anti-inflammation in this context.

IntroductionBlood-brain barrier (BBB) dysfunction occurs in Alzheimer's disease (AD). Yet, the stage at which it appears along the AD time course and whether it contributes to neurodegeneration remain unclear.MethodsOlder adults (61 to 90 years) from cognitively normal (CN) to mildly cognitively impaired (CI), enriched for APOE ?4 and amyloid positivity, underwent dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) and diffusion MRI to measure BBB permeability and brain microstructure. Analysis of variance compared BBB permeability according to cognitive status, amyloid beta (Aβ), and APOE4. Linear regressions assessed associations of BBB permeability with brain microstructure and interactions with Aβ and APOE4.ResultsBBB permeability was elevated for APOE4 carriers across the cortical gray matter, with the strongest differences among CN amyloid-negative individuals. Associations between entorhinal BBB permeability and microstructure interacted with Aβ and APOE4, with the strongest relationships in amyloid-positive individuals and APOE4 carriers.DiscussionAPOE4 may drive widespread BBB dysfunction in preclinical AD, which may contribute to neurodegenerative changes early along the AD cascade.HighlightsGray matter blood-brain barrier (BBB) permeability is elevated for APOE4 carriers. APOE4-related BBB breakdown appears in the absence of cognitive decline or amyloid. BBB leakage correlates with entorhinal cortex microstructural injury. Associations with microstructure are strongest for amyloid-positive APOE4 carriers.

Inquiries into properties of brain structure and function have progressed due to developments in magnetic resonance imaging (MRI). To sustain progress in investigating and quantifying neuroanatomical details in vivo, the reliability and validity of brain measurements are paramount. Quality control (QC) is a set of procedures for mitigating errors and ensuring the validity and reliability of brain measurements. Despite its importance, there is little guidance on best QC practices and reporting procedures. The study of hippocampal subfields in vivo is a critical case for QC because of their small size, inter-dependent boundary definitions, and common artifacts in the MRI data used for subfield measurements. We addressed this gap by surveying the broader scientific community studying hippocampal subfields on their views and approaches to QC. We received responses from 37 investigators spanning 10 countries, covering different career stages, and studying both healthy and pathological development and aging. In this sample, 81% of researchers considered QC to be very important or important, and 19% viewed it as fairly important. Despite this, only 46% of researchers reported on their QC processes in prior publications. In many instances, lack of reporting appeared due to ambiguous guidance on relevant details and guidance for reporting, rather than absence of QC. Here, we provide recommendations for correcting errors to maximize reliability and minimize bias. We also summarize threats to segmentation accuracy, review common QC methods, and make recommendations for best practices and reporting in publications. Implementing the recommended QC practices will collectively improve inferences to the larger population, as well as have implications for clinical practice and public health.

The list of Curing Coma Campaign Collaborators included in the Acknowledgements section has been updated. Flora Hammond, Raimund Helbok, and Naomi Niznick have been added to the list. Several spelling errors have been corrected. A revised file has been included.

ObjectiveDevelop a multi-functional imaging system that combines 1.7μm optical coherence tomography/angiography (OCT/OCTA) to accurately interrogate Hereditary Hemorrhagic Telangiectasia (HHT) skin lesions.MethodsThe study involved imaging HHT skin lesions on five subjects including lips, hands, and chest. We assessed the attributes of both HHT lesions and the healthy vasculature around them in these individuals, employing quantifiable measures such as vascular density and diameter. Additionally, we performed scans on an HHT patient who had undergone anti-angiogenic therapy, allowing us to observe changes in vasculature before and after treatment.ResultsThe results from this pilot study demonstrate the feasibility of evaluating the HHT lesion using this novel methodology and suggest the potential of OCTA to noninvasively track HHT lesions over time. The average percentage change in density between HHT patients' lesions and control was 37%. The percentage increase in vessel diameter between lesion and control vessels in HHT patients was 23.21%.ConclusionIn this study, we demonstrated that OCTA, as a functional extension of OCT, can non-invasively scan HHT lesions in vivo. We scanned five subjects with HHT lesions in various areas (lip, ear, finger, and palm) and quantified vascular density and diameter in both the lesions and adjacent healthy tissue. This non-invasive method will permit a more comprehensive examination of HHT lesions.SignificanceThis method of non-invasive imaging could offer new insights into the physiology, management, and therapeutics of HHT-associated lesion development and bleeding.

PurposeThis study assessed the safety and efficacy of transepithelial crosslinking (CXL) using femtosecond (FS) laser-machined epithelial microchannels (MCs) followed by UVA CXL compared to FS laser (NLO CXL) in rabbits.MethodsThe epithelium of 36 rabbits was machined to create 2- by 25-µm MCs at 400 MCs/mm2. Eyes were treated with 1% riboflavin (Rf) solution for 30 minutes, rinsed, and then crosslinked using UVA or NLO CXL. Rabbits were monitored by epithelial staining, optical coherence tomography (OCT) imaging, and esthesiometry. After sacrifice at 2, 4, or 8 weeks, corneas were examined for collagen autofluorescence and immunohistochemistry.ResultsNLO CXL showed no epithelial damage compared to UVA CXL, which produced on average 23.89 ± 5.6 mm2 epithelial defects that healed by day 3. UVA CXL also produced loss of corneal sensitivity averaging 0.83 ± 0.24 cm force to elicit a blink response that persisted for 28 days and remained significantly lower than control or NLO CXL. OCT imaging detected the presence of a demarcation line only following UVA CXL but not NLO CXL.ConclusionsEven with improved transepithelial Rf penetration, UVA CXL resulted in severe epithelial damage, loss of corneal sensitivity, and delayed wound healing persisting for a month. When MCs were paired with NLO CXL, however, these issues were mostly negated. This suggests that MC NLO CXL can achieve a faster visual recovery without postoperative pain or risk of infection.Translational relevanceUVA CXL is a successful procedure, but there is a need for a transepithelial protocol. The combination of MCs and NLO CXL is able to keep the benefits of UVA CXL without causing epithelial damage.

Soft X-ray imaging is a powerful tool to explore the structure of cells, probe material with nanometer resolution, and investigate the energetic phenomena in the universe. Conventional soft X-ray image sensors are by and large Si-based charge coupled devices that suffer from low frame rates, complex fabrication processes, mechanical inflexibility, and required cooling below -60 °C. Here, a soft X-ray photodiode is reported based on low-cost metal halide perovskite with comparable performance to commercial Si-based device. Nanothrough network electrode minimized the optical loss due to the shadowing of insensitive layers, while a multidimensional perovskite heterojunction is generated to reduce the photo-generated carrier loss. This strategy promoted a record quantum efficiency of 8 × 103% without cooling, several orders of magnitude greater than the previously achieved. Flexible and curved soft X-ray imaging arrays are fabricated based on this high-performance device structure, demonstrating stable soft X-ray response and sharp imaging capabilities. This work highlights the low-cost and efficient perovskite photodiode as a strong candidate for the next-generation soft X-ray image sensors.

The magnetic resonance imaging (MRI) Core has been operating since Alzheimer's Disease Neuroimaging Initiative's (ADNI) inception, providing 20 years of data including reliable, multi-platform standardized protocols, carefully curated image data, and quantitative measures provided by expert investigators. The overarching purposes of the MRI Core include: (1) optimizing and standardizing MRI acquisition methods, which have been adopted by many multicenter studies and trials worldwide and (2) providing curated images and numeric summary values from relevant MRI sequences/contrasts to the scientific community. Over time, ADNI MRI has become increasingly complex. To remain technically current, the ADNI MRI protocol has changed substantially over the past two decades. The ADNI 4 protocol contains nine different imaging types (e.g., three dimensional [3D] T1-weighted and fluid-attenuated inversion recovery [FLAIR]). Our view is that the ADNI MRI data are a greatly underutilized resource. The purpose of this paper is to educate the scientific community on ADNI MRI methods and content to promote greater awareness, accessibility, and use. HIGHLIGHTS: The MRI Core provides multi-platform standardized protocols, carefully curated image data, and quantitative analysis by expert groups. The ADNI MRI protocol has undergone major changes over the past two decades to remain technically current. As of April 25, 2024, the following numbers of image series are available: 17,141 3D T1w; 6877 FLAIR; 3140 T2/PD; 6623 GRE; 3237 dMRI; 2846 ASL; 2968 TF-fMRI; and 2861 HighResHippo (see Table 1 for abbreviations). As of April 25, 2024, the following numbers of quantitative analyses are available: FreeSurfer 10,997; BSI 6120; tensor based morphometry (TBM) and TBM-SYN 12,019; WMH 9944; dMRI 1913; ASL 925; TF-fMRI NFQ 2992; and medial temporal subregion volumes 2726 (see Table 4 for abbreviations). ADNI MRI is an underutilized resource that could be more useful to the research community.

Hyperpolarized (HP) 13C MRI has shown promise as a valuable modality for in vivo measurements of metabolism and is currently in human trials at 15 research sites worldwide. With this growth, it is important to adopt standardized data storage practices as it will allow sites to meaningfully compare data. In this paper, we (1) describe data that we believe should be stored and (2) demonstrate pipelines and methods that utilize the Digital Imaging and Communications in Medicine (DICOM) standard. This includes proposing a set of minimum set of information that is specific to HP 13C MRI studies. We then show where the majority of these can be fit into existing DICOM attributes, primarily via the "Contrast/Bolus" module. We also demonstrate pipelines for utilizing DICOM for HP 13C MRI. DICOM is the most common standard for clinical medical image storage and provides the flexibility to accommodate the unique aspects of HP 13C MRI, including the HP agent information but also spectroscopic and metabolite dimensions. The pipelines shown include creating DICOM objects for studies on human and animal imaging systems with various pulse sequences. We also show a python-based method to efficiently modify DICOM objects to incorporate the unique HP 13C MRI information that is not captured by existing pipelines. Moreover, we propose best practices for HP 13C MRI data storage that will support future multi-site trials, research studies, and technical developments of this imaging technique.

BackgroundAs differentiating between lipomas and atypical lipomatous tumors (ALTs) based on imaging is challenging and requires biopsies, radiomics has been proposed to aid the diagnosis. This study aimed to externally and prospectively validate a radiomics model differentiating between lipomas and ALTs on MRI in three large, multi-center cohorts, and extend it with automatic and minimally interactive segmentation methods to increase clinical feasibility.MethodsThree study cohorts were formed, two for external validation containing data from medical centers in the United States (US) collected from 2008 until 2018 and the United Kingdom (UK) collected from 2011 until 2017, and one for prospective validation consisting of data collected from 2020 until 2021 in the Netherlands. Patient characteristics, MDM2 amplification status, and MRI scans were collected. An automatic segmentation method was developed to segment all tumors on T1-weighted MRI scans of the validation cohorts. Segmentations were subsequently quality scored. In case of insufficient quality, an interactive segmentation method was used. Radiomics performance was evaluated for all cohorts and compared to two radiologists.FindingsThe validation cohorts included 150 (54% ALT), 208 (37% ALT), and 86 patients (28% ALT) from the US, UK and NL. Of the 444 cases, 78% were automatically segmented. For 22%, interactive segmentation was necessary due to insufficient quality, with only 3% of all patients requiring manual adjustment. External validation resulted in an AUC of 0.74 (95% CI: 0.66, 0.82) in US data and 0.86 (0.80, 0.92) in UK data. Prospective validation resulted in an AUC of 0.89 (0.83, 0.96). The radiomics model performed similar to the two radiologists (US: 0.79 and 0.76, UK: 0.86 and 0.86, NL: 0.82 and 0.85).InterpretationThe radiomics model extended with automatic and minimally interactive segmentation methods accurately differentiated between lipomas and ALTs in two large, multi-center external cohorts, and in prospective validation, performing similar to expert radiologists, possibly limiting the need for invasive diagnostics.FundingHanarth fonds.

We proposed an end-to-end deep learning convolutional neural network (DCNN) for region-of-interest based multi-parameter quantification (RMQ-Net) to accelerate quantitative ultrashort echo time (UTE) MRI of the knee joint with automatic multi-tissue segmentation and relaxometry mapping. The study involved UTE-based T1 (UTE-T1) and Adiabatic T1ρ (UTE-AdiabT1ρ) mapping of the knee joint of 65 human subjects, including 20 normal controls, 29 with doubtful-minimal osteoarthritis (OA), and 16 with moderate-severe OA. Comparison studies were performed on UTE-T1 and UTE-AdiabT1ρ measurements using 100%, 43%, 26%, and 18% UTE MRI data as the inputs and the effects on the prediction quality of the RMQ-Net. The RMQ-net was modified and retrained accordingly with different combinations of inputs. Both ROI-based and voxel-based Pearson correlation analyses were performed. High Pearson correlation coefficients were achieved between the RMQ-Net predicted UTE-T1 and UTE-AdiabT1ρ results and the ground truth for segmented cartilage with acceleration factors ranging from 2.3 to 5.7. With an acceleration factor of 5.7, the Pearson r-value achieved 0.908 (ROI-based) and 0.945 (voxel-based) for UTE-T1, and 0.733 (ROI-based) and 0.895 (voxel-based) for UTE-AdiabT1ρ, correspondingly. The results demonstrated that RMQ-net can significantly accelerate quantitative UTE imaging with automated segmentation of articular cartilage in the knee joint.

IntroductionIn academic breast surgery, ultrasound use tends to be limited to radiology departments, thus formal surgical resident training in breast ultrasound is sparse. Building on residents' ultrasound skills in our general surgery training program, we developed a novel curriculum to teach ultrasound-guided breast procedures (UGBPs), including core needle biopsy (CNB) and wire localization (WL). We hypothesized that learning UGBPs on cadavers would be preferred to learning with a breast phantom model using chicken breasts.MethodsResidents received a 1-h lecture on breast CNB and WL followed by a 1-h hands-on laboratory session. Olives stuffed with red pimentos were used to replicate breast masses and implanted in chicken breasts and the breasts of lightly embalmed and unembalmed female cadavers. All residents practiced UGBPs with a course instructor on both models. Residents completed anonymous prelaboratory and postlaboratory surveys utilizing five-point Likert scales.ResultsA total of 35 trainees participated in the didactics; all completed the prelaboratory survey and 28 completed the postlaboratory survey. Participant clinical year ranged from 1 to 6. Residents' confidence in describing and performing CNBs and WLs increased significantly on postlaboratory surveys, controlling for clinical year (P

Pregnancy is a period of profound hormonal and physiological changes experienced by millions of women annually, yet the neural changes unfolding in the maternal brain throughout gestation are not well studied in humans. Leveraging precision imaging, we mapped neuroanatomical changes in an individual from preconception through 2 years postpartum. Pronounced decreases in gray matter volume and cortical thickness were evident across the brain, standing in contrast to increases in white matter microstructural integrity, ventricle volume and cerebrospinal fluid, with few regions untouched by the transition to motherhood. This dataset serves as a comprehensive map of the human brain across gestation, providing an open-access resource for the brain imaging community to further explore and understand the maternal brain.

By age 40 years, over 90% of adults with Down syndrome have Alzheimer's disease pathology and most progress to dementia. Despite having few systemic vascular risk factors, individuals with Down syndrome have elevated cerebrovascular disease markers that track with the clinical progression of Alzheimer's disease, suggesting a role of cerebrovascular disease that is hypothesized to be mediated by inflammatory factors. This study examined the pathways through which small vessel cerebrovascular disease contributes to Alzheimer's disease-related pathophysiology and neurodegeneration in adults with Down syndrome. One hundred eighty-five participants from the Alzheimer's Biomarkers Consortium-Down Syndrome [mean (SD) age = 45.2 (9.3) years] with available MRI and plasma biomarker data were included in this study. White matter hyperintensity (WMH) volumes were derived from T2-weighted fluid-attenuated inversion recovery MRI scans, and plasma biomarker concentrations of amyloid beta 42/40, phosphorylated tau 217, astrocytosis (glial fibrillary acidic protein) and neurodegeneration (neurofilament light chain) were measured with ultrasensitive immunoassays. We examined the bivariate relationships of WMH, amyloid beta 42/40, phosphorylated tau 217 and glial fibrillary acidic protein with age-residualized neurofilament light chain across Alzheimer's disease diagnostic groups. A series of mediation and path analyses examined statistical pathways linking WMH and Alzheimer's disease pathophysiology to promote neurodegeneration in the total sample and groups stratified by clinical diagnosis. There was a direct and indirect bidirectional effect through the glial fibrillary acidic protein of WMH on phosphorylated tau 217 concentration, which was associated with neurofilament light chain concentration in the entire sample. Amongst cognitively stable participants, WMH was directly and indirectly, through glial fibrillary acidic protein, associated with phosphorylated tau 217 concentration, and in those with mild cognitive impairment, there was a direct effect of WMH on phosphorylated tau 217 and neurofilament light chain concentrations. There were no associations of WMH with biomarker concentrations among those diagnosed with dementia. The findings from this cross-sectional study suggest that among individuals with Down syndrome, cerebrovascular disease promotes neurodegeneration by increasing astrocytosis and tau pathophysiology in the presymptomatic phases of Alzheimer's disease, but future studies will need to confirm these associations with longitudinal data. This work joins an emerging literature that implicates cerebrovascular disease and its interface with neuroinflammation as a core pathological feature of Alzheimer's disease in adults with Down syndrome.

IntroductionWe investigated the associations of leptin markers with cognitive function and magnetic resonance imaging (MRI) measures of brain atrophy and vascular injury in healthy middle-aged adults.MethodsWe included 2262 cognitively healthy participants from the Framingham Heart Study with neuropsychological evaluation; of these, 2028 also had available brain MRI. Concentrations of leptin, soluble leptin receptor (sOB-R), and their ratio (free leptin index [FLI]), indicating leptin bioavailability, were measured using enzyme-linked immunosorbent assays. Cognitive and MRI measures were derived using standardized protocols.ResultsHigher sOB-R was associated with lower fractional anisotropy (FA, β = -0.114 ± 0.02, p

IntroductionTau-positron emission tomography (PET) outcome data of patients with Alzheimer's disease (AD) cannot currently be meaningfully compared or combined when different tracers are used due to differences in tracer properties, instrumentation, and methods of analysis.MethodsUsing head-to-head data from five cohorts with tau PET radiotracers designed to target tau deposition in AD, we tested a joint propagation model (JPM) to harmonize quantification (units termed "CenTauR" [CTR]). JPM is a statistical model that simultaneously models the relationships between head-to-head and anchor point data. JPM was compared to a linear regression approach analogous to the one used in the amyloid PET Centiloid scale.ResultsA strong linear relationship was observed between CTR values across brain regions. Using the JPM approach, CTR estimates were similar to, but more accurate than, those derived using the linear regression approach.DiscussionPreliminary findings using the JPM support the development and adoption of a universal scale for tau-PET quantification.HighlightsTested a novel joint propagation model (JPM) to harmonize quantification of tau PET. Units of common scale are termed "CenTauRs". Tested a Centiloid-like linear regression approach. Using five cohorts with head-to-head tau PET, JPM outperformed linearregressionbased approach. Strong linear relationship was observed between CenTauRs values across brain regions.

BackgroundThis study compares positive margin rates in breast conserving surgery (BCS) for early breast cancer using two localization techniques: surgeon-performed intraoperative ultrasound-guided wire localization (IOWL) versus radiologist-performed preoperative wire localization (POWL).MethodsPatients with unifocal breast cancer undergoing BCS with follow-up at a single institution were retrospectively identified. Factors associated with positive margins were identified.Results177 patients underwent IOWL (N ​= ​85) or POWL (N ​= ​92). There was a significantly lower rate of positive margins for IOWL vs. POWL (7.1 ​% vs. 23.9 ​%, p ​= ​0.002) and a corresponding lower rate of re-excision for IOWL vs. POWL (5.9 ​% vs. 18.5 ​%, p ​= ​0.011). Presence of DCIS was associated with positive margins (p ​= ​0.015). After adjusting for presence of DCIS, tumor size, and volume of tissue removed, the positive margin rate was significantly lower in the IOWL group compared to the POWL group (aOR 0.34, 95 ​% CI 0.13-0.93).ConclusionsIn this study, adjusted analysis favored IOWL in achieving negative tumor margins. Prospective studies are needed to further explore the impact of IOWL on quality, cost-effectiveness, and patient experience.

COVID-19 is associated with increased risk for cognitive decline but very little is known regarding the neural mechanisms of this risk. We enrolled 49 adults (55% female, mean age = 30.7 ± 8.7), 25 with and 24 without a history of COVID-19 infection. We administered standardized tests of cognitive function and acquired brain connectivity data using MRI. The COVID-19 group demonstrated significantly lower cognitive function (W = 475, p

Photo-sono therapy (PST) is an innovative anti-vascular approach based on cavitation-induced spallation. Currently, passive cavitation detection (PCD) is the prevalent technique for cavitation monitoring during treatment. However, the limitations of PCD are the lack of spatial information of bubbles and the difficulty of integration with the PST system. To address this, we proposed a new, to the best of our knowledge, cavitation mapping method that integrates Doppler optical coherence tomography (OCT) with PST to visualize bubble dynamics in real time. The feasibility of the proposed system has been confirmed through experiments on vascular-mimicking phantoms and in vivo rabbit ear vessels, and the results are compared to high-speed camera observations and PCD data. The findings demonstrate that Doppler OCT effectively maps cavitation in real time and holds promise for guiding PST treatments and other cavitation-related clinical applications.

We have conducted a search for strong gravitational lensing systems in the Dark Energy Spectroscopic Instrument (DESI) Legacy Imaging Surveys Data Release 9. This is the third paper in a series. These surveys together cover ∼19,000 deg2 visible from the Northern Hemisphere, reaching a z-band AB magnitude of ∼22.5. We use a deep residual neural network, trained on a compilation of known lensing systems and high-grade candidates as well as nonlenses in the same footprint. After applying our trained neural network to the survey data, we visually inspect and rank images with probabilities above a threshold which has been chosen to balance precision and recall. We have found 1895 lens candidates, of which 1512 are identified for the first time. Combining the discoveries from this work with those from Papers I (335) and II (1210), we have discovered a total of 3057 new candidates in the Legacy Surveys.

BackgroundThe impression section integrates key findings of a radiology report but can be subjective and variable. We sought to fine-tune and evaluate an open-source Large Language Model (LLM) in automatically generating impressions from the remainder of a radiology report across different imaging modalities and hospitals.MethodsIn this institutional review board-approved retrospective study, we collated a dataset of CT, US, and MRI radiology reports from the University of California San Francisco Medical Center (UCSFMC) (n = 372,716) and the Zuckerberg San Francisco General (ZSFG) Hospital and Trauma Center (n = 60,049), both under a single institution. The Recall-Oriented Understudy for Gisting Evaluation (ROUGE) score, an automatic natural language evaluation metric that measures word overlap, was used for automatic natural language evaluation. A reader study with five cardiothoracic radiologists was performed to more strictly evaluate the model's performance on a specific modality (CT chest exams) with a radiologist subspecialist baseline. We stratified the results of the reader performance study based on the diagnosis category and the original impression length to gauge case complexity.ResultsThe LLM achieved ROUGE-L scores of 46.51, 44.2, and 50.96 on UCSFMC and upon external validation, ROUGE-L scores of 40.74, 37.89, and 24.61 on ZSFG across the CT, US, and MRI modalities respectively, implying a substantial degree of overlap between the model-generated impressions and impressions written by the subspecialist attending radiologists, but with a degree of degradation upon external validation. In our reader study, the model-generated impressions achieved overall mean scores of 3.56/4, 3.92/4, 3.37/4, 18.29 s,12.32 words, and 84 while the original impression written by a subspecialist radiologist achieved overall mean scores of 3.75/4, 3.87/4, 3.54/4, 12.2 s, 5.74 words, and 89 for clinical accuracy, grammatical accuracy, stylistic quality, edit time, edit distance, and ROUGE-L score respectively. The LLM achieved the highest clinical accuracy ratings for acute/emergent findings and on shorter impressions.ConclusionsAn open-source fine-tuned LLM can generate impressions to a satisfactory level of clinical accuracy, grammatical accuracy, and stylistic quality. Our reader performance study demonstrates the potential of large language models in drafting radiology report impressions that can aid in streamlining radiologists' workflows.

High-resolution peripheral quantitative computed tomography (HR-pQCT) has emerged as a powerful imaging technique for characterizing bone microarchitecture in the human peripheral skeleton. The second-generation HR-pQCT scanner provides improved spatial resolution and a shorter scan time. However, the transition from the first-generation (XCTI) to second-generation HR-pQCT scanners (XCTII) poses challenges for longitudinal studies, multi-center trials, and comparison to historical data. Cross-calibration, an established approach for determining relationships between measurements obtained from different devices, can bridge this gap and enable the utilization and comparison of legacy data. The goal of this study was to establish cross-calibration equations to estimate XCTII measurements from XCTI data, using both the standard and Laplace-Hamming (LH) binarization approaches. Thirty-six volunteers (26-85 yr) were recruited and their radii and tibiae were scanned on both XCTI and XCTII scanners. XCTI images were analyzed using the manufacturer's standard protocol. XCTII images were analyzed twice: using the manufacturer's standard protocol and the LH segmentation approach previously developed and validated by our team. Linear regression analysis was used to establish cross-calibration equations. Results demonstrated strong correlations between XCTI and XCTII density and geometry outcomes. For most microstructural outcomes, although there were considerable differences in absolute values, correlations between measurements obtained from different scanners were strong, allowing for accurate cross-calibration estimations. For some microstructural outcomes with a higher sensitivity to spatial resolution (eg, trabecular thickness, cortical pore diameter), XCTII standard protocol resulted in poor correlations between the scanners, while our LH approach improved these correlations and decreased the difference in absolute values and the proportional bias for other measurements. For these reasons and due to the improved accuracy of our LH approach compared with the standard approach, as established in our previous study, we propose that investigators should use the LH approach for analyzing XCTII scans, particularly when comparing to XCTI data.

Meningiomas are associated with inactivation of NF2/Merlin, but approximately one-third of meningiomas with favorable clinical outcomes retain Merlin expression. Biochemical mechanisms underlying Merlin-intact meningioma growth are incompletely understood, and non-invasive biomarkers that may be used to guide treatment de-escalation or imaging surveillance are lacking. Here, we use single-cell RNA sequencing, proximity-labeling proteomic mass spectrometry, mechanistic and functional approaches, and magnetic resonance imaging (MRI) across meningioma xenografts and patients to define biochemical mechanisms and an imaging biomarker that underlie Merlin-intact meningiomas. We find Merlin serine 13 (S13) dephosphorylation drives meningioma Wnt signaling and tumor growth by attenuating inhibitory interactions with β-catenin and activating the Wnt pathway. MRI analyses show Merlin-intact meningiomas with S13 phosphorylation and favorable clinical outcomes are associated with high apparent diffusion coefficient (ADC). These results define mechanisms underlying a potential imaging biomarker that could be used to guide treatment de-escalation or imaging surveillance for patients with Merlin-intact meningiomas.

PurposeSGLT2, the sodium glucose cotransporter two, is expressed in human pancreatic, prostate and brain tumors, and in a mouse cancer model SGLT2 inhibitors reduce tumor glucose uptake and growth. In this study we have measured the effect of a specific SGLT2 inhibitor, Jardiance® (Empagliflozin), on glucose uptake into astrocytomas in patients.MethodsWe have used a specific SGLT glucose tracer, α-methyl-4-[18F]fluoro-4-deoxy-α-D-glucopyranoside (Me4FDG), and Positron Emission Tomography (PET) to measure glucose uptake. Four of five patients enrolled had WHO grade IV glioblastomas, and one had a low grade WHO Grade II astrocytoma. Two dynamic brain PET scans were conducted on each patient, one before and one after treatment with a single oral dose of Jardiance, a specific SGLT2 inhibitor. As a control, we also determined the effect of oral Jardiance on renal SGLT2 activity.ResultsIn all five patients an oral dose (25 or 100 mg) of Jardiance reduced Me4FDG tumor accumulation, highly significant inhibition in four, and inhibited SGLT2 activity in the kidney.ConclusionsThese initial experiments show that SGLT2 is a functional glucose transporter in astocytomas, and Jardiance inhibited glucose uptake, a drug approved by the FDA to treat type 2 diabetes mellitus (T2DM), heart failure, and renal failure. We suggest that clinical trials be initiated to determine whether Jardiance reduces astrocytoma growth in patients.

Tumor acidosis is one of the hallmarks indicating the initiation and progression of various cancers. Here, we present a protocol for preparing a hyperpolarized (HP) 13C-bicarbonate tissue pH MRI imaging contrast agent to detect aggressive tumors. We describe the steps for the formulation and polarization of a precursor molecule 13C-glycerol carbonate (13C-GLC), the post-dissolution reaction, and converting HP 13C-GLC to an injectable HP 13C-bicarbonate solution. We then detail procedures for MRI data acquisition to generate tumor pH maps for assessing tumor aggressiveness. For complete details on the use and execution of this protocol, please refer to Mu et al.1.

IntroductionModic changes (MC) are bone marrow lesions of vertebral bones, which can be detected with magnetic resonance imaging (MRI) adjacent to degenerated intervertebral discs. Defined by their appearance on T1 and T2 weighted images, there are three interconvertible types: MC1, MC2, and MC3. The inter-observer variability of the MRI diagnosis is high, therefore a diagnostic serum biomarker complementing the MRI to facilitate diagnosis and follow-up would be of great value.MethodsWe used a highly sensitive and reproducible proteomics approach: DIA/SWATH-MS to find serum biomarkers in a subset of the Northern Finland Birth Cohort 1966. Separately, we measured a panel of factors involved in inflammation and angiogenesis to confirm some potential biomarkers published before with an ELISA-based method called V-Plex.ResultsWe found neither an association between the serum concentrations of the proteins detected with DIA/SWATH-MS with the presence of MC, nor a correlation with the size of the MC lesions. We did not find any association between the factors measured with the V-Plex and the presence of MC or their size.ConclusionAltogether, our study suggests that a robust and generally usable biomarker to facilitate the diagnosis of MC cannot readily be found in serum.

ObjectivesTo investigate image-guided volumetric hyperthermia strategies using the ExAblate Body MR-guided focused ultrasound ablation system, involving mechanical transducer movement and sector-vortex beamforming.Materials and methodsAcoustic and thermal simulations were performed to investigate volumetric hyperthermia using mechanical transducer movement combined with sector-vortex beamforming, specifically for the ExAblate Body transducer. The system control in the ExAblate Body system was modified to achieve fast transducer movement and MR thermometry-based hyperthermia control, mechanical transducer movements and electronic sector-vortex beamforming were combined to optimize hyperthermia delivery. The experimental validation was performed using a tissue-mimicking phantom.ResultsThe developed simulation framework allowed for a parametric study with varying numbers of heating spots, sonication durations, and transducer movement times to evaluate the hyperthermia characteristics for mechanical transducer movement and sector-vortex beamforming. Hyperthermic patterns involving 2-4 sequential focal spots were analyzed. To demonstrate the feasibility of volumetric hyperthermia in the system, a tissue-mimicking phantom was sonicated with two distinct spots through mechanical transducer movement and sector-vortex beamforming. During hyperthermia, the average values of Tmax, T10, Tavg, T90, and Tmin over 200 s were measured within a circular ROI with a diameter of 10 pixels. These values were found to be 8.6, 7.9, 6.6, 5.2, and 4.5 °C, respectively, compared to the baseline temperature.ConclusionsThis study demonstrated the volumetric hyperthermia capabilities of the ExAblate Body system. The simulation framework developed in this study allowed for the evaluation of hyperthermia characteristics that could be implemented with the ExAblate MRgFUS system.

Background and objectivesAmyloid pathology, vascular disease pathology, and pathologies affecting the medial temporal lobe are associated with cognitive trajectories in older adults. However, only limited evidence exists on how these pathologies influence cognition in the oldest old. We evaluated whether amyloid burden, white matter hyperintensity (WMH) volume, and hippocampal volume (HV) are associated with cognitive level and decline in the oldest old.MethodsThis was a longitudinal, observational community-based cohort study. We included participants with 18F-florbetapir PET and MRI data from the 90+ Study. Amyloid load was measured using the standardized uptake value ratio in the precuneus/posterior cingulate with eroded white matter mask as reference. WMH volume was log-transformed. All imaging measures were standardized using sample means and SDs. HV and log-WMH volume were normalized by total intracranial volume using the residual approach. Global cognitive performance was measured by the Mini-Mental State Examination (MMSE) and modified MMSE (3MS) tests, repeated every 6 months. We used linear mixed-effects models with random intercepts; random slopes; and interaction between time, time squared, and imaging variables to estimate the associations of imaging variables with cognitive level and cognitive decline. Models were adjusted for demographics, APOE genotype, and health behaviors.ResultsThe sample included 192 participants. The mean age was 92.9 years, 125 (65.1%) were female, 71 (37.0%) achieved a degree beyond college, and the median follow-up time was 3.0 years. A higher amyloid load was associated with a lower cognitive level (βMMSE = -0.82, 95% CI -1.17 to -0.46; β3MS = -2.77, 95% CI -3.69 to -1.84). A 1-SD decrease in HV was associated with a 0.70-point decrease in the MMSE score (95% CI -1.14 to -0.27) and a 2.27-point decrease in the 3MS score (95% CI -3.40 to -1.14). Clear nonlinear cognitive trajectories were detected. A higher amyloid burden and smaller HV were associated with faster cognitive decline. WMH volume was not significantly associated with cognitive level or decline.DiscussionAmyloid burden and hippocampal atrophy are associated with both cognitive level and cognitive decline in the oldest old. Our findings shed light on how different pathologies contributed to driving cognitive function in the oldest old.

The design and optimization of laser-Compton x-ray systems based on compact distributed charge accelerator structures can enable micron-scale imaging of disease and the concomitant production of beams of Very High Energy Electrons (VHEEs) capable of producing FLASH-relevant dose rates. The physics of laser-Compton x-ray scattering ensures that the scattered x-rays follow exactly the trajectory of the incident electrons, thus providing a route to image-guided, VHEE FLASH radiotherapy. The keys to a compact architecture capable of producing both laser-Compton x-rays and VHEEs are the use of X-band RF accelerator structures which have been demonstrated to operate with over 100 MeV/m acceleration gradients. The operation of these structures in a distributed charge mode in which each radiofrequency (RF) cycle of the drive RF pulse is filled with a low-charge, high-brightness electron bunch is enabled by the illumination of a high-brightness photogun with a train of UV laser pulses synchronized to the frequency of the underlying accelerator system. The UV pulse trains are created by a patented pulse synthesis approach which utilizes the RF clock of the accelerator to phase and amplitude modulate a narrow band continuous wave (CW) seed laser. In this way it is possible to produce up to 10 μA of average beam current from the accelerator. Such high current from a compact accelerator enables production of sufficient x-rays via laser-Compton scattering for clinical imaging and does so from a machine of "clinical" footprint. At the same time, the production of 1000 or greater individual micro-bunches per RF pulse enables > 10 nC of charge to be produced in a macrobunch of < 100 ns. The design, construction, and test of the 100-MeV class prototype system in Irvine, CA is also presented.

Background: Computed tomography (CT) is the preferred imaging modality for bone evaluation of the knee, while MRI of the bone is actively being developed. We present three techniques using short-interval delta ultrashort echo time (δUTE), field echo (FE), and FE with high resolution–deep learning reconstruction (HR–DLR) for direct bone MRI. Methods: Knees of healthy volunteers (n = 5, 3 females, 38 ± 17.2 years old) were imaged. CT-like images were generated by averaging images from multiple echoes and inverting. The bone signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) were determined. Results: The δUTE depicted a cortical bone with high signal intensity but could not resolve trabeculae. In contrast, both the FE and FE HR–DLR images depicted cortical and trabecular bone with high signal. Quantitatively, while δUTE had a good bone SNR of ~100 and CNR of ~40 for the cortical bone, the SNR for the FE HR–DLR was significantly higher (p < 0.05), at over 400, and CNR at over 200. Conclusions: For 3D rendering of the bone surfaces, the δUTE provided better image contrast and separation of bone from ligaments and tendons than the FE sequences. While there still is no MRI technique that provides a perfect CT-like contrast, continued advancement of MRI techniques may provide benefits for specific use cases.

IntroductionThe understanding of the pathological events in Alzheimer's disease (AD) has advanced dramatically, but the successful translation from rodent models into efficient human therapies is still problematic.MethodsTo examine how tau pathology can develop in the primate brain, we injected 12 macaques with a dual tau mutation (P301L/S320F) into the entorhinal cortex (ERC). An investigation was performed using high-resolution microscopy, magnetic resonance imaging (MRI), positron emission tomography (PET), and fluid biomarkers to determine the temporal progression of the pathology 3 and 6 months after the injection.ResultsUsing quantitative microscopy targeting markers for neurodegeneration and neuroinflammation, as well as fluid and imaging biomarkers, we detailed the progression of misfolded tau spreading and the consequential inflammatory response induced by glial cells.DiscussionBy combining the analysis of several in vivo biomarkers with extensive brain microscopy analysis, we described the initial steps of misfolded tau spreading and neuroinflammation in a monkey model highly translatable to AD patients.HighlightsDual tau mutation delivery in the entorhinal cortex induces progressive tau pathology in rhesus macaques. Exogenous human 4R-tau coaptates monkey 3R-tau during transneuronal spread, in a prion-like manner. Neuroinflammatory response is coordinated by microglia and astrocytes in response to tau pathology, with microglia targeting early tau pathology, while astrocytes engaged later in the progression, coincident with neuronal death. Monthly collection of CSF and plasma revealed a profile of changes in several AD core biomarkers, reflective of neurodegeneration and neuroinflammation as early as 1 month after injection.

We present a new method to measure sub-microcurie activities of photon-emitting radionuclides in organs and lesions of small animals in vivo. Our technique, named the collimator-less likelihood fit, combines a very high sensitivity collimatorless detector with a Monte Carlo-based likelihood fit in order to estimate the activities in previously segmented regions of interest along with their uncertainties. This is done directly from the photon projections in our collimatorless detector and from the region of interest segmentation provided by an x-ray computed tomography scan. We have extensively validated our approach with 225Ac experimentally in spherical phantoms and mouse phantoms, and also numerically with simulations of a realistic mouse anatomy. Our method yields statistically unbiased results with uncertainties smaller than 20% for activities as low as ~111Bq (3nCi) and for exposures under 30 minutes. We demonstrate that our method yields more robust recovery coefficients when compared to SPECT imaging with a commercial pre-clinical scanner, specially at very low activities. Thus, our technique is complementary to traditional SPECT/CT imaging since it provides a more accurate and precise organ and tumor dosimetry, with a more limited spatial information. Finally, our technique is specially significant in extremely low-activity scenarios when SPECT/CT imaging is simply not viable.

Background Intravenous prostate-specific membrane antigen (PSMA)-targeted radioligand therapy improves survival in men with metastatic castration-resistant prostate cancer. Yet, the impact of selective prostatic arterial administration on primary tumor uptake is unclear. Purpose To compare gallium 68 (68Ga)-PSMA-11 uptake using dynamic PET/CT in prostatic tumoral volumes of interest (VOIs) during intravenous and selective prostatic arterial infusions for individuals with untreated, high-risk prostate cancer. Materials and Methods In this prospective, intraindividual comparative study conducted at an academic medical center, five men aged 58, 61, 64, 66, and 68 years with treatment-naive prostate cancer were enrolled between January 2022 and February 2023 and underwent two dynamic 68Ga-PSMA-11 PET/CT examinations 1 week apart. During the first examination, the radiotracer was administered intravenously. During the second administration, the radiotracer was delivered into either the right or left prostatic artery through an angiographically placed microcatheter. The primary outcome was maximum standardized uptake value (SUVmax) in prostatic tumoral VOIs. The secondary outcomes included mean SUV (SUVmean) in prostatic tumoral VOIs and area under the SUVmean curves (AUC). Longitudinal mixed-effects models were used to compare dynamic SUVmax and SUVmean time-activity curves (TACs), and paired t tests were used for the remaining data. Results The mean SUVmax within tumoral VOIs was 14 (range, 3-43) for venous sessions and 938 (range, 460-1436) for arterial sessions (P = .008). The SUVmean within VOIs was greater during arterial sessions (P < .001) overall and 46-fold and 19-fold greater at peak uptake and final time points, respectively. The mean AUC was greater on arterial TACs than on venous TACs at 14600 SUV × min (range, 8353-20025 SUV × min) and 240 SUV × min (range, 69-622 SUV × min), respectively (P = .002). Conclusion Selective prostatic arterial infusion resulted in greater 68Ga-PSMA-11 tumoral SUV than intravenous infusion. Further study of local-regional, intra-arterial delivery of a PSMA-targeted theranostic agent is warranted in high-risk prostate cancer. ClinicalTrials.gov identifier: NCT04976257 © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Civelek in this issue.

A single dose of psilocybin, a psychedelic that acutely causes distortions of space-time perception and ego dissolution, produces rapid and persistent therapeutic effects in human clinical trials1-4. In animal models, psilocybin induces neuroplasticity in cortex and hippocampus5-8. It remains unclear how human brain network changes relate to subjective and lasting effects of psychedelics. Here we tracked individual-specific brain changes with longitudinal precision functional mapping (roughly 18 magnetic resonance imaging visits per participant). Healthy adults were tracked before, during and for 3 weeks after high-dose psilocybin (25 mg) and methylphenidate (40 mg), and brought back for an additional psilocybin dose 6-12 months later. Psilocybin massively disrupted functional connectivity (FC) in cortex and subcortex, acutely causing more than threefold greater change than methylphenidate. These FC changes were driven by brain desynchronization across spatial scales (areal, global), which dissolved network distinctions by reducing correlations within and anticorrelations between networks. Psilocybin-driven FC changes were strongest in the default mode network, which is connected to the anterior hippocampus and is thought to create our sense of space, time and self. Individual differences in FC changes were strongly linked to the subjective psychedelic experience. Performing a perceptual task reduced psilocybin-driven FC changes. Psilocybin caused persistent decrease in FC between the anterior hippocampus and default mode network, lasting for weeks. Persistent reduction of hippocampal-default mode network connectivity may represent a neuroanatomical and mechanistic correlate of the proplasticity and therapeutic effects of psychedelics.

BackgroundRadiation delivery with ultra-high dose rate (FLASH) radiotherapy (RT) holds promise for improving treatment outcomes and reducing side effects but poses challenges in radiation delivery accuracy due to its ultra-high dose rates. This necessitates the development of novel imaging and verification technologies tailored to these conditions.PurposeOur study explores the effectiveness of proton-induced acoustic imaging (PAI) in tracking the Bragg peak in three dimensions and in real time during FLASH proton irradiations, offering a method for volumetric beam imaging at both conventional and FLASH dose rates.MethodsWe developed a three-dimensional (3D) PAI technique using a 256-element ultrasound detector array for FLASH dose rate proton beams. In the study, we tested protoacoustic signal with a beamline of a FLASH-capable synchrocyclotron, setting the distal 90% of the Bragg peak around 35 mm away from the ultrasound array. This configuration allowed us to assess various total proton radiation doses, maintaining a consistent beam output of 21 pC/pulse. We also explored a spectrum of dose rates, from 15 Gy/s up to a FLASH rate of 48 Gy/s, by administering a set number of pulses. Furthermore, we implemented a three-dot scanning beam approach to observe the distinct movements of individual Bragg peaks using PAI. All these procedures utilized a proton beam energy of 180 MeV to achieve the maximum possible dose rate.ResultsOur findings indicate a strong linear relationship between protoacoustic signal amplitudes and delivered doses (R2 = 0.9997), with a consistent fit across different dose rates. The technique successfully provided 3D renderings of Bragg peaks at FLASH rates, validated through absolute Gamma index values.ConclusionsThe protoacoustic system demonstrates effectiveness in 3D visualization and tracking of the Bragg peak during FLASH proton therapy, representing a notable advancement in proton therapy quality assurance. This method promises enhancements in protoacoustic image guidance and real-time dosimetry, paving the way for more accurate and effective treatments in ultra-high dose rate therapy environments.

AimsAccurate cardiac chamber quantification is essential for clinical decisions and ideally should be consistent across different echocardiography systems. This study evaluates variations between the Philips EPIQ CVx (version 9.0.3) and Canon Aplio i900 (version 7.0) in measuring cardiac volumes, ventricular function, and valve structures.Methods and resultsIn this gender-balanced, single-centre study, 40 healthy volunteers (20 females and 20 males) aged 40 years and older (mean age 56.75 ± 11.57 years) were scanned alternately with both systems by the same sonographer using identical settings for both 2D and 4D acquisitions. We compared left ventricular (LV) and right ventricular (RV) volumes using paired t-tests, with significance set at P < 0.05. Correlation and Bland-Altman plots were used for quantities showing significant differences. Two board-certified cardiologists evaluated valve anatomy for each platform. The results showed no significant differences in LV end-systolic volume and LV ejection fraction between platforms. However, LV end-diastolic volume (LVEDV) differed significantly (biplane: P = 0.018; 4D: P = 0.028). Right ventricular (RV) measurements in 4D showed no significant differences, but there were notable disparities in 2D and 4D volumes within each platform (P < 0.01). Significant differences were also found in the LV systolic dyssynchrony index (P = 0.03), LV longitudinal strain (P = 0.04), LV twist (P = 0.004), and LV torsion (P = 0.005). Valve structure assessments varied, with more abnormalities noted on the Philips platform.ConclusionAlthough LV and RV volumetric measurements are generally comparable, significant differences in LVEDV, LV strain metrics, and 2D vs. 4D measurements exist. These variations should be considered when using different platforms for patient follow-ups.

Isthmic spondylolysis is characterized by a stress injury to the pars interarticularis bones of the lumbar spines and is often missed by conventional magnetic resonance imaging (MRI), necessitating a computed tomography (CT) for accurate diagnosis. We compare MRI techniques suitable for producing CT-like images. Lumbar spines of asymptomatic and low back pain (LBP) subjects were imaged at 3-Tesla with multi-echo ultrashort echo time (UTE) and field echo (FE) sequences followed by simple post-processing of averaging and inverting to depict spinal bones with a CT-like appearance. The contrast-to-noise ratio (CNR) for bone was determined to compare UTE vs. FE and single-echo vs. multi-echo data. Visually, both sequences depicted cortical bone with good contrast; UTE-processed sequences provided a flatter contrast for soft tissues that made them easy to distinguish from bone, while FE-processed images had better resolution and bone–muscle contrast, which are important for fracture detection. Additionally, multi-echo images provided significantly (p = 0.03) greater CNR compared with single-echo images. Using these techniques, progressive spondylolysis was detected in an LBP subject. This study demonstrates the feasibility of using spine bone MRI to yield CT-like contrast. Through the employment of multi-echo UTE and FE sequences combined with simple processing, we observe sufficient enhancements in image quality and contrast to detect pars fractures.

PurposeThe aim of this study is to prospectively evaluate whether women with copper-containing intrauterine devices (Cu-IUD), currently listed as MR conditional, can safely undergo 3.0 Tesla (3 T) magnetic resonance imaging (MRI).Methods73 women, age 18-54 years old, with a Cu-IUD who were undergoing MRI for any reason were included consecutively. Pre- and post-MRI standard pelvic ultrasound examinations were completed to determine the appropriate pre- and post-MRI positioning of the Cu-IUD. Displaced IUDs were defined by IUD crossbars not in the fundal portion of the endometrial cavity, a visualized tip in the mid or lower uterus, any part of the device located in the cervical canal or outside of the endometrial canal, a fractured device, or a non-visualized IUD. Additionally, a questionnaire was completed by participants to determine the level of pre- and post-MRI pelvic pain.ResultsThere were zero observed displaced Cu-IUDs on post-MRI pelvic ultrasounds (p = 0/70, 95% CI 0, .043). Three participants were dropped from the study due to malpositioned IUDs on pre-MRI pelvic ultrasound. Six patients reported new or worsening pelvic pain/discomfort during or after their MRI examination.ConclusionOur results suggest that performing 3 T MRI using a low SAR setting does not cause displacement of Cu-IUDs, with zero out of 70 patients demonstrating IUD displacement.

Tracking gene expression in deep tissues requires genetic reporters that can be unambiguously detected using tissue penetrant techniques. Magnetic resonance imaging (MRI) is uniquely suited for this purpose; however, there is a dearth of reporters that can be reliably linked to gene expression with minimal interference from background tissue signals. Here, we present a conceptually new method for generating background-subtracted, drug-gated, multiplex images of gene expression using MRI. Specifically, we engineered chemically erasable reporters consisting of a water channel, aquaporin-1, fused to destabilizing domains, which are stabilized by binding to cell-permeable small-molecule ligands. We showed that this approach allows for highly specific detection of gene expression through differential imaging. In addition, by engineering destabilized aquaporin-1 variants with orthogonal ligand requirements, it is possible to distinguish distinct subpopulations of cells in mixed cultures. Finally, we demonstrated this approach in a mouse tumor model through differential imaging of gene expression with minimal background.

The kidney is the most common solid organ transplant globally and rates continue to climb, driven by the increasing prevalence of end stage renal disease (ESRD). Compounded by advancements in surgical techniques and immunosuppression leading to longer graft survival, radiologists evermore commonly evaluate kidney transplant patients and candidates, underscoring their role along the transplant process. Multiphase computed tomography (CT) with multiplanar and 3D reformatting is the primary method for evaluating renal donor candidates, detailing renal size, vascular/collecting system anatomy, and identifying significant pathologies such as renal vascular diseases and nephrolithiasis. Ultrasound is the preferred initial postoperative imaging modality for graft evaluation due to its low cost, accessibility, noninvasiveness, and lack of radiation. CT and magnetic resonance imaging (MRI) may be useful adjunctive imaging techniques in diagnosing transplant pathology when ultrasound alone is not diagnostic. Kidney transplant complications are categorized by an approximate timeline framework, aiding in differential diagnosis based on onset, duration, and severity and include perinephric fluid collections, graft compression, iatrogenic injuries, vascular compromise, graft rejection, and neoplastic processes. This review discusses imaging strategies and important findings along the transplant timeline, from donor assessment to long-term recipient complications.

PurposeTo compare rates of retinal nerve fiber layer change over time in healthy, eyes with nonprogressing glaucoma and eyes with progressing glaucoma using single wide-field (SWF) and optic nerve head (ONH) cube scan optical coherence tomography (OCT) images.MethodsForty-five eyes of 25 healthy individuals and 263 eyes of 161 glaucoma patients from the Diagnostic Innovations in Glaucoma Study were included. All eyes underwent 24-2 visual field testing and OCT (Spectralis SD-OCT) ONH and macular imaging. SWF images (up to 43° × 28°) were created by stitching together ONH cube scans centered on the optic disc and macular cube scans centered on the fovea. Visual field progression was defined as guided progression analysis likely progression and/or a significant (P < 0.01) mean deviation slope of less than -1.0 dB/year. Mixed effects models were used to compare rates of change. Highly myopic eyes were included.ResultsThirty glaucomatous eyes were classified as progressing. In eyes with glaucoma, mean global rate of change was -1.22 µm/year (P < 0.001) using SWF images and -0.83 µm/year (P = 0.003) using ONH cube scans. Rate of change was significantly greater in eyes with progressing glaucoma compared with eyes with nonprogressing glaucoma (-1.51 µm/year vs. -1.24 µm/year; P = 0.002) using SWF images and was similar using ONH cube scans (P = 0.27).ConclusionsIn this cohort that includes eyes with and without high axial myopia, the mean rate of retinal nerve fiber layer thinning measured using SWF images was faster in eyes with progressing glaucoma than in eyes with nonprogressing glaucoma. Wide-field OCT images including the ONH and macula can be effective for monitoring glaucomatous progression in patients with and without high myopia.

BackgroundPort-Wine Birthmarks (PWB) are congenital capillary malformations requiring multiple treatments. Optical coherence tomography (OCT), a noninvasive imaging technique, characterizes vessels in cutaneous vascular lesions, including PWBs.ObjectiveTo assess variability in blood vessel characteristics within and between individual PWBs.MethodsOCT was used to measure blood vessel density (%) and modal vessel diameter (micrometers) at increments of 0.05 mm from the skin surface to a depth of 0.50 mm at several adjacent spots of single PWBs in this cross-sectional study. Average ratios of vessel density and diameter in affected to control skin were obtained for each PWB by averaging data for all spots within a lesion. Statistical analysis was performed with a linear mixed effects model using SPSS software (IBM Corporation).ResultsThere was great variability in vessel density and diameter within and between PWBs. Depths where average ratios of vessel density were consistently greater in affected to control skin were shallow, between 0.15 mm and 0.2 mm deep from the skin surface.LimitationsSmall sample size and device's inability to measure diameters smaller than 20 micrometers.ConclusionThere is variability in vessel density and diameter within and between PWBs. Individualized treatment planning guided by OCT mapping should be studied further.

Theories of psychotic illness suggest that abnormal intrinsic functional connectivity may explain its characteristic positive and disorganization symptoms as well as lead to impaired general functioning. Here we used resting state functional magnetic resonance imaging (fMRI) to evaluate associations between these symptoms and the degree to which global connectivity is abnormal in early psychosis (EP). Eighty-six healthy controls (HCs) and 108 individuals with EP with resting state fMRI data were included in primary analyses. The EP group included 83 participants with schizophrenia-spectrum disorders and 25 with bipolar disorder type I with psychotic features. A global intrinsic connectivity "similarity index" for each EP individual was determined by calculating its correlation with the average HC connectivity matrix extracted using Schaefer atlases of multiple parcellations (100, 200, 300, and 400 region parcellations). As hypothesized, connectivity similarity with the average HC matrix was negatively associated with Brief Psychiatric Rating Scale total score, Scale for the Assessment of Positive Symptoms total score, and disorganization symptoms. Similarity was also positively associated with Global Assessment of Functioning score. Results were not driven by sex or diagnosis effects and were consistent across parcellation schemes. These results support the hypothesis that changes in whole-brain connectivity patterns are associated with psychosis symptoms and support the use of functional connectivity as a biomarker for these symptoms in EP.

The Hispanic/Latino population is one of the largest and most diverse ethnoracial groups in the United States at high risk for dementia. We examined cognitive constructs and associations with subsequent hippocampal volume (HV) and white matter hyperintensity volume (WMHV). Participants were from the Hispanic Community Health Study/Study of Latinos-Magnetic Resonance Imaging Study (n = 2029). We examined confirmatory factor analysis and longitudinal invariance using neurocognitive scores at Visits 1 (2008-2011) and 2 (2014-2018) and path analyses. We obtained a longitudinally invariant two-factor episodic memory (EM) and working memory (WM) construct. Lower EM profile at both visits was associated with greater WMHV and smaller HV at Visit 2. Lower WM profile at both visits was associated with larger WMHV and smaller HV at Visit 2. Neurocognitive profiles were associated with subsequent neurodegeneration in a sample of Hispanics/Latinos. Identifying neurocognitive risk profiles may lead to early detection and intervention, and significantly impact the course of neurodegeneration.HighlightsCognitive profiles predict brain integrity up to 10 years later.We observed two-factor latent memory constructs and longitudinal invariance.These findings were observed in a Hispanic/Latino cohort.