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BackgroundSchizophrenia is considered a polygenic disorder. People with schizophrenia and those with genetic high risk of schizophrenia (GHR) have presented with similar neurodevelopmental deficits in hemispheric asymmetry. The potential associations between neurodevelopmental abnormalities and schizophrenia-related risk genes in both schizophrenia and those with GHR remains unclear.AimsTo investigate the shared and specific alternations to the structural network in people with schizophrenia and those with GHR. And to identify an association between vulnerable structural network alternation and schizophrenia-related risk genes.MethodA total of 97 participants with schizophrenia, 79 participants with GHR and 192 healthy controls, underwent diffusion tensor imaging (DTI) scans at a single site. We used graph theory to characterise hemispheric and whole-brain structural network topological metrics. For 26 people in the schizophrenia group and 48 in the GHR group with DTI scans we also calculated their schizophrenia-related polygenic risk scores (SZ-PRSs). The correlations between alterations to the structural network and SZ-PRSs were calculated. Based on the identified genetic–neural association, bioinformatics enrichment was explored.ResultsThere were significant hemispheric asymmetric deficits of nodal efficiency, global and local efficiency in the schizophrenia and GHR groups. Hemispheric asymmetric deficit of local efficiency was significantly positively correlated with SZ-PRSs in the schizophrenia and GHR groups. Bioinformatics enrichment analysis showed that these risk genes may be linked to signal transduction, neural development and neuron structure. The schizophrenia group showed a significant decrease in the whole-brain structural network.ConclusionsThe shared asymmetric deficits in people with schizophrenia and those with GHR, and the association between anomalous asymmetry and SZ-PRSs suggested a vulnerability imaging marker regulated by schizophrenia-related risk genes. Our findings provide new insights into asymmetry regulated by risk genes and provides a better understanding of the genetic–neural pathological underpinnings of schizophrenia.

Significance: Intraplaque hemorrhage (IPH) is an important indicator of plaque vulnerability. Early detection could aid the prevention of stroke. Aim: We aim to detect IPH with single wavelength PA imaging in vivo and to improve image quality. Approach: We developed a singular value decomposition (SVD)-based filter to detect the nonstationary and stationary components in ultrasound data. A PA mask was created to detect stationary (IPH) sources. The method was tested ex vivo using phantoms and in vivo in patients. Results: The flow and IPH channels were successfully separated in the phantom data. We can also detect the PA signals from IPH and reject signals from the carotid lumen in vivo. Generalized contrast-to-noise ratio improved in both ex vivo and in vivo in US imaging. Conclusions: SVD-based filtering can successfully detect IPH using a single laser wavelength, opening up opportunities for more economical and cost-effective laser sources.

Significance: Photoacoustic imaging (PAI) is a powerful emerging technology with broad clinical applications, but consensus test methods are needed to standardize performance evaluation and accelerate translation. Aim: To review consensus image quality test methods for mature imaging modalities [ultrasound, magnetic resonance imaging (MRI), x-ray CT, and x-ray mammography], identify best practices in phantom design and testing procedures, and compare against current practices in PAI phantom testing. Approach: We reviewed scientific papers, international standards, clinical accreditation guidelines, and professional society recommendations describing medical image quality test methods. Observations are organized by image quality characteristics (IQCs), including spatial resolution, geometric accuracy, imaging depth, uniformity, sensitivity, low-contrast detectability, and artifacts. Results: Consensus documents typically prescribed phantom geometry and material property requirements, as well as specific data acquisition and analysis protocols to optimize test consistency and reproducibility. While these documents considered a wide array of IQCs, reported PAI phantom testing focused heavily on in-plane resolution, depth of visualization, and sensitivity. Understudied IQCs that merit further consideration include out-of-plane resolution, geometric accuracy, uniformity, low-contrast detectability, and co-registration accuracy. Conclusions: Available medical image quality standards provide a blueprint for establishing consensus best practices for photoacoustic image quality assessment and thus hastening PAI technology advancement, translation, and clinical adoption.

Significance: Diffuse optical tomography (DOT) uses near-infrared light spectroscopy (NIRS) to measure changes in cerebral hemoglobin concentration. Anatomical interpretations of NIRS data require accurate descriptions of the cranio-cerebral relations and DOT sensitivity to the underlying cortical structures. Such information is limited for pediatric populations because they undergo rapid head and brain development. Aim: We aim to investigate age-related differences in scalp-to-cortex distance and mapping between scalp locations and cortical regions of interest (ROIs) among infants (2 weeks to 24 months with narrow age bins), children (4 and 12 years), and adults (20 to 24 years). Approach: We used spatial scalp projection and photon propagation simulation methods with age-matched realistic head models based on MRIs. Results: There were age-group differences in the scalp-to-cortex distances in infancy. The developmental increase was magnified in children and adults. There were systematic age-related differences in the probabilistic mappings between scalp locations and cortical ROIs. Conclusions: Our findings have important implications in the design of sensor placement and making anatomical interpretations in NIRS and fNIRS research. Age-appropriate, realistic head models should be used to provide anatomical guidance for standalone DOT data in infants.

The first two years of human life are characterized by the most dynamic growth in brain structures1–5 and remarkable cognitive and behavioral changes.6,7 Functional near-infrared spectroscopy (fNIRS; a list of abbreviations is provided in Table S1 in the Supplementary Material for the convenience of the reader) is an irreplaceable neuroimaging tool for studying early brain functional development, providing unprecedented opportunities for recording the hemodynamic response in awake, behaving infants because of its balanced temporal-spatial resolution and resilience to movement.8–11 Notably, although the Centers for Disease Control and Prevention defines 0- to 1-year-olds (yo) and 2- to 3-yo children as infants and toddlers, respectively, we have described 0- to 2-yo children as infants in this study for readability. Despite the suitability of fNIRS in infant studies, a major limitation of this technique is the inability of fNIRS data to provide structural information of the head tissue. In fNIRS measurements, a source–detector (SD) pair positioned on the scalp surface measures local concentration changes in oxygenated and deoxygenated hemoglobin caused by neural activity.12–15 On the other hand, while neural activity tied to a specific human function originates in local brain regions. The absence of structural information in the fNIRS signal makes it impossible to correlate the signal response with the anatomical brain regions. Therefore, in fNIRS studies, the scalp location where the SD pair is attached to its underlying brain region where the fNIRS signal originates should be mapped. We call this mapping the scalp-cortex correlation (SCC). Several methods for obtaining SCC have been proposed for studies on adults; however, only a few studies have provided SCC for the infant population. Similar to adults, infant SCC is mostly based on a simple geometrical technique, i.e., correlating the location of the SD pair on the scalp, typically, the midpoint of the SD pair, with cortical regions in a simple point-to-point geometrical manner. For instance, researchers often referred to the international 10-20 or 10-10 system16 when attaching SD pairs on the scalp and then inferred the anatomical locations17–19 according to the geometrical SCC of the adult head20,21 or infant head.22–25 Notably, by linearly reducing the size of the adult heads, the virtual registration method26 has also been employed to estimate SCC in infant studies.27–29 As described above, the point-to-point geometrical SCC provides a tolerable estimation of the underlying brain regions for the absorption change acquired by the SD pair. Nevertheless, the geometrical SCC is based on the assumption that the absorption change occurs at the cortical projection point below the midpoint between the SD pair, and light scattering in the head tissue is not considered. Mounting evidence from light propagation analysis in the adult head revealed light scattering in the head tissue could have a considerable influence on the partial pathlength (PPL) in the brain and the spatial sensitivity profile (SSP).30–34 Notably, a few studies have already demonstrated that light propagation in the infant heads is distinct from that in adults owing to structural differences.35,36 Furthermore, very recent studies on adults have started considering light propagation in turbid media when calculating the SCC.37,38 However, to date, no light propagation analysis-based SCC data are available for 0- to 2-yo infants. In addition to age, SD distance must have a significant influence on optics-based SCC during early development. Only a few studies have examined the effect of SD distance on fNIRS sensitivity in infant brain tissue.35,39 For example, Fukui et al.35 found that fNIRS sensitivity to gray matter (GM) and white matter (WM) of neonates was modulated by the SD distance. These threads of evidence revealed that it remains largely unknown how age and SD distance affect optics-based SCC in 0- to 2-yo infants and how to choose an appropriate SD distance to ensure both the sensitivity to cerebral hemodynamics and the selectivity of signals from a specific brain region of interest. To address these issues, the current study aimed to create a precise optics-based SCC between SD pairs on the scalp fiducial point and brain regions defined by a macro-anatomical atlas by considering the light scattering in 0-, 1-, and 2-yo infant heads. In addition, we quantitatively characterized the changes in SCC with age and SD distance and evaluated the suitable SD distances for each age. The optics-based SCC was obtained for each SD pair by solving the diffusion equation.

Optical coherence tomography (OCT) is one of the most innovative and successfully translated imaging techniques with substantial clinical and economic impacts and acceptance.1,2 OCT is a non-invasive optical analog to ultrasound (US) with significantly higher resolution ( millions of A-scans/s) imaging with tissue penetration of up to 2 mm, closely matching that of conventional histopathology. The year 2021 marks not only the 30th birthday of OCT (assuming its initiation with the Science paper by Huang et al.3 in 1991) but also the 35th birthday of low-coherence interferometry and optical ranging in biological systems.4,5 In the last three decades, more than 75,000 OCT related papers have been published (about two thirds in ophthalmology) with continuous yearly increases of published articles.6 Breaking through the 1000 publications/year barrier was initiated in 2005/2006 with the introduction of spectral domain OCT (SD OCT). In 2020, the OCT-related scientific output was more than 7800 papers, resulting in nearly one paper every single hour on every single day of the year. Extrapolating this publishing performance, a saturation of yearly publication output at about 9500 can be expected around 2030. After 30 years, it is interesting and important to benchmark this performance with other medical imaging techniques:6 multiphoton microscopy (MPM) [including second harmonic generation (SHG) and third harmonic generation (THG)], developed about three decades before OCT,7,8 has about 50,000 publications so far; photoacoustic imaging (PAI), established in the 1970s,9,10 has about 15,000 papers; and confocal microscopy, developed in the 1940s,11,12 has about 145,000. Developed in the 1940s,13 US imaging has contributed to about 160,000 papers; positron emission tomography (PET), initiated in the 1970s,14,15 has about 175,000; computed tomography (CT), developed in the 1930s,16 has about 750,000; and magnetic resonance imaging (MRI), developed in the late 1940s,17 has close to 1,000,000 publications. This dominance in publications of radiology and nuclear medicine imaging technologies is also one of the reasons why medical imaging is, in general, associated with MRI, CT, PET, or US. It is important to note, though, that from a medical imaging market perspective, optical imaging technologies dominate with 66% versus 34% for radiology and nuclear medicine imaging technologies. In addition, in the United States alone, about 450,000 physicians use primarily optical imaging techniques; 60,000 use primarily radiologic imaging; and about 130,000 use both.18 In the last three decades, OCT has revolutionized ophthalmic diagnosis, therapy monitoring, and guidance. Every second, a human gets a retinal OCT scan; therefore it is the fastest adopted imaging technology in the history of ophthalmology. This is mainly due to the ease of optical accessibility of the human eye, OCT’s exquisite depth sectioning performance at the micrometer level, and a significantly better performance compared with the previous gold standard in this field, ultrasonography. Furthermore, it is also due to the fact that the human retina cannot be biopsied and finally to the continuous clinically relevant improvements of this technology, due to an exquisite ecosystem between industry and academia in terms of resolution, speed, wide-field imaging, and longer wavelength for choroidal imaging. Motion contrast-based angiography, cellular level retinal visualization, visible light OCT for oximetry and unprecedented retinal layer detection, functional and contrast enhanced extensions, and artificial intelligence (AI)-enhanced performance also contributed to this success. Most of these superb technological developments can be directly translated to the original motivation and idea of OCT: to enable optical biopsy, i.e., the in situ imaging of tissue microstructure with a resolution approaching that of histology but without the need for tissue excision and preparation, allowing for quasi-instantaneous diagnostic feedback for physicians, and thereby reducing healthcare costs. There is no doubt that outside ophthalmology, OCT faces significantly bigger challenges with extremely well performing, long-established diagnostic techniques. Hence, OCT has successfully penetrated into different medical fields outside of ophthalmology, but in the last 30 years, it has not been as successful as in ophthalmic diagnosis. Despite the unprecedented success of this imaging technique in ophthalmology so far, there are still numerous remaining challenges in this field to be addressed (e.g., 4D intrasurgical OCT, portable, handheld OCT, and OCT-based digital adaptive optics) but one of the biggest perspectives for OCT is to further push performance frontiers of all involved technologies to converge to the original motivation of OCT, which is to enable in situ optical biopsy, especially for early cancer diagnosis and for a better understanding of oncogenesis. Consequently, this perspective will focus on the following areas that will pave the way for enabling even further enhanced medical diagnosis using OCT in the future. Imaging speed is absolutely essential in medical diagnosis: on the one hand, to minimize the exam time for the patient, but foremost to enable motion artifact free, properly sampled data sets. The speed of today’s systems already supports three- and even four-dimensional imaging as well as wide fields of view and functional extensions of OCT, such as OCT angiography. In the future, different technologies will enable increased OCT imaging speed with one of the fundamental decisions being at which scanning speed single-beam raster scanning will be abandoned and scanning beam parallelization will be used. Further challenges of OCT’s unmatched axial and transverse resolution will also be discussed. Similar to combining different radiology and nuclear medicine imaging technologies in current clinical diagnosis, multimodal optical imaging not only enables the “best of both/all worlds” but also compensates for the deficits of OCT (metabolic, molecular sensitivity, penetration depth, and limited contrast). Multimodal imaging applications combining techniques complementary to OCT will more and more be transferred from significantly improved microscopy setups—acting as fast quasi-histological optical biopsies next to the operating room—to the miniaturized endoscopic level with OCT acting like a global positioning system (GPS) by prescreening the tissue at a wider field of view (FOV) with microscopic resolution. Aside from OCTA, no other functional or contrast enhancing OCT extension has accomplished comparable clinical impact in the last three decades. Some more recently developed ones that might accomplish this challenging task, including quantitative OCTA (especially in neuro-ophthalmology), optical coherence elastography (OCE), dynamic contrast OCT, oximetry using visible light OCT, optophysiology—also referred to optoretinography—and AI-enhanced OCT, will be covered in this perspective. In addition, OCT miniaturization for portable, compact, handheld OCT applications, as well as for home-OCT and self-OCT, will be discussed. Finally, industrial translation of OCT, including medical device regulatory challenges, will be reviewed.

Cerium oxide nanoparticles with integrated gadolinium have been proved to be useful as contrast agents in magnetic resonance imaging. Of question is their performance in dual-energy computed tomography. The aims of this work are to determine (1) the relation between the computed tomography number and the concentration of the I, Gd or Ce contrast agent and (2) under what conditions it is possible to resolve the type of contrast agent. Hounsfield values of iodoacetic acid, gadolinium acetate and cerium acetate dissolved in water at molar concentrations of 10, 50 and 100 mM were measured in a water phantom using the Siemens SOMATOM Definition Force scanner; gadolinium- and cerium acetate were used as substitutes for the gadolinium-integrated cerium oxide nanoparticles. The relation between the molar concentration of the I, Gd or Ce contrast agent and the Hounsfield value was linear. Concentrations had to be sufficiently high to resolve the contrast agents. Funding: VetenskapsradetSwedish Research Council [VR-NT 2016-05033]

Purpose: Convolutional neural network (CNN) methods have been proposed to quantify lesions in medical imaging. Commonly, more than one imaging examination is available for a patient, but the serial information in these images often remains unused. CNN-based methods have the potential to extract valuable information from previously acquired imaging to better quantify lesions on current imaging of the same patient. Approach: A pretrained CNN can be updated with a patient’s previously acquired imaging: patient-specific fine-tuning (FT). In this work, we studied the improvement in performance of lesion quantification methods on magnetic resonance images after FT compared to a pretrained base CNN. We applied the method to two different approaches: the detection of liver metastases and the segmentation of brain white matter hyperintensities (WMH). Results: The patient-specific fine-tuned CNN has a better performance than the base CNN. For the liver metastases, the median true positive rate increases from 0.67 to 0.85. For the WMH segmentation, the mean Dice similarity coefficient increases from 0.82 to 0.87. Conclusions: We showed that patient-specific FT has the potential to improve the lesion quantification performance of general CNNs by exploiting a patient’s previously acquired imaging.

Purpose: Hippocampus contouring for radiotherapy planning is performed on MR image data due to poor anatomical visibility on computed tomography (CT) data. Deep learning methods for direct CT hippocampus auto-segmentation exist, but use MR-based training contours. We investigate if these can be replaced by CT-based contours without loss in segmentation performance. This would remove the MR not only from inference but also from training. Approach: The hippocampus was contoured by medical experts on MR and CT data of 45 patients. Convolutional neural networks (CNNs) for hippocampus segmentation on CT were trained on CT-based or propagated MR-based contours. In both cases, their predictions were evaluated against the MR-based contours considered as the ground truth. Performance was measured using several metrics, including Dice score, surface distances, and contour Dice score. Bayesian dropout was used to estimate model uncertainty. Results: CNNs trained on propagated MR contours (median Dice 0.67) significantly outperform those trained on CT contours (0.59) and also experts contouring manually on CT (0.59). Differences between the latter two are not significant. Training on MR contours results in lower model uncertainty than training on CT contours. All contouring methods (manual or CNN) on CT perform significantly worse than a CNN segmenting the hippocampus directly on MR (median Dice 0.76). Additional data augmentation by rigid transformations improves the quantitative results but the difference remains significant. Conclusions: CT-based training contours for CT hippocampus segmentation cannot replace propagated MR-based contours without significant loss in performance. However, if MR-based contours are used, the resulting segmentations outperform experts in contouring the hippocampus on CT.

Significance: Researchers have made great progress in single-image super-resolution (SISR) using deep convolutional neural networks. However, in the field of leukocyte imaging, the performance of existing SISR methods is still limited as it fails to thoroughly explore the geometry and structural consistency of leukocytes. The inaccurate super-resolution (SR) results will hinder the pathological study of leukocytes, since the structure and cell lineage determine the types of leukocyte and will significantly affect the subsequent inspection. Aim: We propose a deep network that takes full use of the geometry prior and structural consistency of the leukocyte images. We establish and annotate a leukocyte dataset, which contains five main types of leukocytes (basophil, eosinophil, monocyte, lymphocyte, and neutrophil), for learning the structure and geometry information. Approach: Our model is composed of two modules: prior network and SR network. The prior network estimates the parsing map of the low-resolution (LR) image, and then the SR network takes both the estimated parsing map and LR image as input to predict the final high-resolution image. Result: Experiments show that the geometry prior and structural consistency in use obviously improves the SR performance of leukocyte images, enhancing the peak-signal-to-noise ratio (PSNR) by about 0.4 dB in our benchmark. Conclusion: As proved by our leukocyte SR benchmark, the proposed method significantly outperforms state-of-the-art SR methods. Our method not only improves the PSNR and structural similarity indices, but also accurately preserves the structural details of leukocytes. The proposed method is believed to have potential use in the wide-field cell prescreening by simply using a low-power objective.

Significance: Functional near-infrared spectroscopy (fNIRS) is an emerging brain imaging technique due to its small size, low cost, minimum scanning sonic noise, and portability. Unfortunately, because this technique does not provide neuroanatomical information to accompany the functional data, its data interpretation remains a persistent challenge in fNIRS brain imaging applications. The two most popular approaches for fNIRS anatomical registration are magnetic resonance imaging (MRI) and three-dimensional (3-D) digitization. MRI scanning yields high-precision registration but reduces the cost-effectiveness and accessibility of fNIRS imaging. Alternatively, the low cost and portable 3-D digitizers are affected by magnetic properties of ambient metal objects, including participant clothing, testing equipment, medical implants, and so forth. Aim: To overcome these obstacles and provide accessible and reliable neuroanatomical registration for fNIRS imaging, we developed and explored a photogrammetry optode registration (POR) method. Approach: The POR method uses a consumer-grade camera to reconstruct a 3-D image of the fNIRS optode-set, including light emitters and detectors, on a participant’s head. This reconstruction process uses a linear-time incremental structure from motion (LTI-SfM) algorithm, based on 100 to 150 digital photos. The POR method then aligns the reconstructed image with an anatomical template of the brain. Results: To validate this method, we tested 22 adult and 19 child participants using the POR method and MRI imaging. The results comparisons suggest on average 55% and 46% overlap across all data channel measurements registered by the two methods in adult and children, respectively. Importantly, this overlap reached 65% and 60% in only the frontal channels. Conclusions: These results suggested that the mismatch in registration was partially due to higher variation in backward optode placement rather than the registration efficacy. Therefore, the photo-based registration method can offer an accessible and reliable approach to neuroanatomical registration of fNIRS as well as other surface-based neuroimaging and neuromodulation methods.

The specific role of the corpus callosum (CC) in language network organization remains unclear, two contrasting models have been proposed: inhibition of homotopic areas allowing for independent functioning of the hemispheres versus integration of information from both hemispheres. This study aimed to add to this discussion with the first investigation of language network connectivity in combination with CC volume measures. In 38 healthy children aged 6–12, we performed task‐based functional magnetic resonance imaging to measure language network connectivity, used structural magnetic resonance imaging to quantify CC subsection volumes, and administered various language tests to examine language abilities. We found an increase in left intrahemispheric and bilateral language network connectivity and a decrease in right intrahemispheric connectivity associated with larger volumes of the posterior, mid‐posterior, and central subsections of the CC. Consistent with that, larger volumes of the posterior parts of the CC were significantly associated with better verbal fluency and vocabulary, the anterior CC volume was positively correlated with verbal span. Thus, children with larger volumes of CC subsections showed increased interhemispheric language network connectivity and were better in different language domains. This study presents the first evidence that the CC is directly linked to language network connectivity and underlines the excitatory role of the CC in the integration of information from both hemispheres., In 38 healthy children aged 6–12, the present study measured language network connectivity, corpus callosum subsection volumes, and language abilities. Children with larger volumes of CC subsections showed increased interhemispheric language network connectivity and were better in different language domains. The present study suggests that the corpus callosum is directly linked to language network connectivity and underlines the excitatory role of the corpus callosum in the integration of information from both hemispheres. .

Significance: Fluorescence guidance in cancer surgery (FGS) using molecular-targeted contrast agents is accelerating, yet the influence of individual patients’ physiology on the optimal time to perform surgery post-agent-injection is not fully understood. Aim: Develop a mathematical framework and analytical expressions to estimate patient-specific time-to-maximum contrast after imaging agent administration for single- and paired-agent (coadministration of targeted and control agents) protocols. Approach: The framework was validated in mouse subcutaneous xenograft studies for three classes of imaging agents: peptide, antibody mimetic, and antibody. Analytical expressions estimating time-to-maximum-tumor-discrimination potential were evaluated over a range of parameters using the validated framework for human cancer parameters. Results: Correlations were observed between simulations and matched experiments and metrics of tumor discrimination potential (p15 h for antibodies, on average. The analytical estimates of time-to-maximum tumor discrimination performance exhibited errors of

Purpose: Our study predictively maps epithelium density in magnetic resonance imaging (MRI) space while varying the ground truth labels provided by five pathologists to quantify the downstream effects of interobserver variability. Approach: Clinical imaging and postsurgical tissue from 48 recruited prospective patients were used in our study. Tissue was sliced to match the MRI orientation and whole-mount slides were stained and digitized. Data from 28 patients (n = 33 slides) were sent to five pathologists to be annotated. Slides from the remaining 20 patients (n = 123 slides) were annotated by one of the five pathologists. Interpathologist variability was measured using Krippendorff’s alpha. Pathologist-specific radiopathomic mapping models were trained using a partial least-squares regression using MRI values to predict epithelium density, a known marker for disease severity. An analysis of variance characterized intermodel means difference in epithelium density. A consensus model was created and evaluated using a receiver operator characteristic classifying high grade versus low grade and benign, and was statistically compared to apparent diffusion coefficient (ADC). Results: Interobserver variability ranged from low to acceptable agreement (0.31 to 0.69). There was a statistically significant difference in mean predicted epithelium density values (p

SignificanceMajor depressive disorder (MDD) affects over 40 million US adults in their lifetimes. Transcranial photobiomodulation (t-PBM) has been shown to be effective in treating MDD, but the current treatment dosage does not account for anatomical head and brain changes due to aging.AimWe study effective t-PBM dosage and its variations across age groups using state-of-the-art Monte Caxrlo (MC) simulations and age-dependent brain atlases ranging between 5 to 85 years of age.ApproachAge-dependent brain models are derived from 18 MRI brain atlases. Two extracranial source positions, F3-F4 and Fp1-Fpz-Fp2 in the EEG 10-20 system, are simulated at five selected wavelengths and energy depositions at two MDD-relevant cortical regions – dorsolateral prefrontal cortex (dlPFC) and ventromedial prefrontal cortex (vmPFC) – are quantified.ResultsAn overall decrease of energy deposition was found with increasing age. A strong negative correlation between the thickness of extra-cerebral tissues (ECT) and energy deposition, suggesting that increasing ECT thickness over age is primarily responsible for reduced energy delivery. The F3-F4 position appears to be more efficient in reaching dlPFC compared to treating vmPFC via the Fp1-Fpz-Fp2 position.ConclusionQuantitative simulations revealed age-dependent light delivery across the lifespan of human brains, suggesting the needs for personalized and age-adaptive t-PBM treatment planning.

Purpose: Reconstruction of patient anatomy is critical to patient-specific instrument (PSI) design in total joint replacement (TJR). Conventionally, computed tomography (CT) and magnetic resonance imaging (MRI) are used to obtain the patient anatomy as they are accurate imaging modalities. However, computing anatomical landmarks from the patient anatomy for PSIs requires either high-resolution CT, increasing time of scan and radiation exposure to the patient, or longer and more expensive MRI scans. As an alternative, reconstruction from single-plane fluoroscopic x-ray provides a cost-efficient tool to obtain patient anatomical structures while allowing capture of the patient’s joint dynamics, important clinical information for TJR. Approach: We present a three-dimensional (3D) reconstruction scheme that automatically and accurately reconstructs the 3D knee anatomy from single-plane fluoroscopic x-ray based on a nonlinear statistical shape model called kernel principal component analysis. To increase robustness, we designed a hybrid energy function that integrated feature and intensity information as a similarity measure for the 3D reconstruction. Results: We evaluated the proposed method on five subjects during deep knee bending: the root-mean-square accuracy is 1.19±0.36 mm for reconstructed femur and 1.15±0.17 mm for reconstructed tibia. Conclusions: The proposed method demonstrates reliable 3D bone model reconstruction accuracy with successful elimination of prior 3D imaging and reduction of manual labor and radiation dose on patient as well as characterizing joints in motion. This method is promising for applications in medical interventions such as patient-specific arthroplasty design, surgical planning, surgical navigation, and understanding anatomical and dynamic characteristics of joints.

An MR-Linac can provide motion information of tumour and organs-at-risk before, during, and after beam delivery. However, MR imaging cannot provide real-time high-quality volumetric images which capture breath-to-breath variability of respiratory motion. Surrogate-driven motion models relate the motion of the internal anatomy to surrogate signals, thus can estimate the 3D internal motion from these signals. Internal surrogate signals based on patient anatomy can be extracted from 2D cine-MR images, which can be acquired on an MR-Linac during treatment, to build and drive motion models. In this paper we investigate different MRI-derived surrogate signals, including signals generated by applying principal component analysis to the image intensities, or control point displacements derived from deformable registration of the 2D cine-MR images. We assessed the suitability of the signals to build models that can estimate the motion of the internal anatomy, including sliding motion and breath-to-breath variability. We quantitatively evaluated the models by estimating the 2D motion in sagittal and coronal slices of 8 lung cancer patients, and comparing them to motion measurements obtained from image registration. For sagittal slices, using the first and second principal components on the control point displacements as surrogate signals resulted in the highest model accuracy, with a mean error over patients around 0.80 mm which was lower than the in-plane resolution. For coronal slices, all investigated signals except the skin signal produced mean errors over patients around 1 mm. These results demonstrate that surrogate signals derived from 2D cine-MR images, including those generated by applying principal component analysis to the image intensities or control point displacements, can accurately model the motion of the internal anatomy within a single sagittal or coronal slice. This implies the signals should also be suitable for modelling the 3D respiratory motion of the internal anatomy.

To tackle the problem of magnetic resonance imaging (MRI)-only radiotherapy treatment planning (RTP), we propose a multi-atlas information propagation scheme that jointly segments organs and generates pseudo x-ray computed tomography (CT) data from structural MR images (T1-weighted and T2-weighted). As the performance of the method strongly depends on the quality of the atlas database composed of multiple sets of aligned MR, CT and segmented images, we also propose a robust way of registering atlas MR and CT images, which combines structure-guided registration, and CT and MR image synthesis. We first evaluated the proposed framework in terms of segmentation and CT synthesis accuracy on 15 subjects with prostate cancer. The segmentations obtained with the proposed method were compared using the Dice score coefficient (DSC) to the manual segmentations. Mean DSCs of 0.73, 0.90, 0.77 and 0.90 were obtained for the prostate, bladder, rectum and femur heads, respectively. The mean absolute error (MAE) and the mean error (ME) were computed between the reference CTs (non-rigidly aligned to the MRs) and the pseudo CTs generated with the proposed method. The MAE was on average \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{upgreek} \usepackage{mathrsfs} \setlength{\oddsidemargin}{-69pt} \begin{document} }{}$45.7\pm 4.6$ \end{document}45.7±4.6 HU and the ME \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{upgreek} \usepackage{mathrsfs} \setlength{\oddsidemargin}{-69pt} \begin{document} }{}$-1.6\pm 7.7$ \end{document}−1.6±7.7 HU. We then performed a dosimetric evaluation by re-calculating plans on the pseudo CTs and comparing them to the plans optimised on the reference CTs. We compared the cumulative dose volume histograms (DVH) obtained for the pseudo CTs to the DVH obtained for the reference CTs in the planning target volume (PTV) located in the prostate, and in the organs at risk at different DVH points. We obtained average differences of \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{upgreek} \usepackage{mathrsfs} \setlength{\oddsidemargin}{-69pt} \begin{document} }{}$-0.14 \% $ \end{document}−0.14% in the PTV for \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{upgreek} \usepackage{mathrsfs} \setlength{\oddsidemargin}{-69pt} \begin{document} }{}${{D}_{98 \% }}$ \end{document}D98%, and between \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{upgreek} \usepackage{mathrsfs} \setlength{\oddsidemargin}{-69pt} \begin{document} }{}$-0.14 \% $ \end{document}−0.14% and 0.05% in the PTV, bladder, rectum and femur heads for Dmean and \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{upgreek} \usepackage{mathrsfs} \setlength{\oddsidemargin}{-69pt} \begin{document} }{}${{D}_{2 \% }}$ \end{document}D2%. Overall, we demonstrate that the proposed framework is able to automatically generate accurate pseudo CT images and segmentations in the pelvic region, potentially bypassing the need for CT scan for accurate RTP.

Noninvasive, three-dimensional, and longitudinal imaging of cerebral blood flow (CBF) in small animal models and ultimately in humans has implications for fundamental research and clinical applications. It enables the study of phenomena such as brain development and learning and the effects of pathologies, with a clear vision for translation to humans. Speckle contrast optical tomography (SCOT) is an emerging optical method that aims to achieve this goal by directly measuring three-dimensional blood flow maps in deep tissue with a relatively inexpensive and simple system. High-density SCOT is developed to follow CBF changes in response to somatosensory cortex stimulation. Measurements are carried out through the intact skull on the rat brain. SCOT is able to follow individual trials in each brain hemisphere, where signal averaging resulted in comparable, cortical images to those of functional magnetic resonance images in spatial extent, location, and depth. Sham stimuli are utilized to demonstrate that the observed response is indeed due to local changes in the brain induced by forepaw stimulation. In developing and demonstrating the method, algorithms and analysis methods are developed. The results pave the way for longitudinal, nondestructive imaging in preclinical rodent models that can readily be translated to the human brain., This project was funded by Fundació CELLEX Barcelona, Ministerio de Economía y Competitividad/FEDER (PHOTODEMENTIA, DPI2015-64358-C2-1-R), Instituto de Salud Carlos III/FEDER (MEDPHOTAGE, DTS16/00087), the “Severo Ochoa” Program for Centers of Excellence in R\&D (SEV-2015-0522), the Obra Social “la Caixa” Foundation (LlumMedBcn), AGAUR-Generalitat (2017 SGR 1380), LASERLAB-EUROPE IV, and “Fundació La Marató TV3.”

Quantitative measures of blood flow and metabolism are essential for improved assessment of brain health and response to ischemic injury. In this report, we demonstrate a multimodal technique for measuring the cerebral metabolic rate of oxygen (CMRO2) in the rodent brain on an absolute scale (μM O2 / min). We use laser speckle imaging (LSI) at 809 nm and spatial frequency domain imaging (SFDI) at 655 nm, 730 nm, and 850 nm to obtain spatiotemporal maps of cerebral blood flow (CBF), tissue absorption (μa), and tissue scattering (μs’). Knowledge of these three values enables calculation of a characteristic blood flow speed, which in turn is input to a mathematical model with a “zero-flow” boundary condition to calculate absolute CMRO2. We apply this method to a rat model of cardiac arrest (CA) and cardiopulmonary resuscitation. With this model, the zero-flow condition occurs during entry into CA. The CMRO2 values calculated with our method are in good agreement with those measured with magnetic resonance (MR) and positron emission tomography (PET) by other groups. Our technique provides a quantitative metric of cerebral metabolism that can potentially be used for comparison between animals and longitudinal monitoring of a single animal over multiple days, to assess differences in baseline metabolism and track recovery of metabolism in survival studies following ischemia and reperfusion.

Interstitial photodynamic therapy (iPDT) with 5-aminolevulinic acid (ALA) is a possible alternative treatment for malignant brain tumors. Further evaluation is, however, required before it can be clinically applied. Computational simulation of the photophysical process in ALA-iPDT can offer a quantitative tool for understanding treatment outcomes, which depend on various variables related to clinical treatment conditions. We propose a clinical simulation method of ALA-iPDT for malignant brain tumors using a singlet oxygen (O12) model and O12 threshold to induce cell death. In this method, the amount of O12 generated is calculated using a photosensitizer photobleaching coefficient and O12 quantum yield, which have been measured in several previous studies. Results of the simulation using clinical magnetic resonance imaging data show the need to specify the insertion positions of cylindrical light diffusers and the level of light fluence. Detailed analysis with a numerical brain tumor model demonstrates that ALA-iPDT treatment outcomes depend on combinations of photobleaching and threshold values. These results indicate that individual medical procedures, including pretreatment planning and treatment monitoring, will greatly benefit from simulation of ALA-iPDT outcomes.

Relatively few imaging and sensing technologies are employed to study human lactation physiology. In particular, human mammary development during pregnancy as well as mammary involution after lactation have been poorly described, despite their importance for breast cancer diagnosis and treatment during these phases. Our case study shows the potential of diffuse optical spectroscopic imaging (DOSI) to uniquely study the spatiotemporal changes in mammary tissue composition during the involution of the lactating breast toward its pre-pregnant state. At nine time intervals over a period of eight months after the cessation of breastfeeding, we reconstructed 2-D maps of mammary water content, lipid content, total hemoglobin (THb) concentration, oxygen saturation (StO2), and tissue optical scattering. Mammary lipid content in the nonareolar region showed a significant relative increase of 59%, whereas water content and THb concentration showed a significant relative decrease of 50% and 48%, respectively. Significant changes were also found in StO2 and tissue optical scattering. Our findings are consistent with the gradual replacement of fibroglandular tissue by adipose tissue and vascular regression during mammary involution. Moreover, our data provide unique insight into the dynamics of breast tissue composition and demonstrate the effectiveness of DOSI as a technique to study human lactation physiology.

MR-guided radiotherapy treatment planning utilises the high soft-tissue contrast of MRI to reduce uncertainty in delineation of the target and organs at risk. Replacing 4D-CT with MRI-derived synthetic 4D-CT would support treatment plan adaptation on hybrid MR-guided radiotherapy systems for inter- and intrafractional differences in anatomy and respiration, whilst mitigating the risk of CT to MRI registration errors. Three methods were devised to calculate synthetic 4D and midposition (time-weighted mean position of the respiratory cycle) CT from 4D-T1w and Dixon MRI. The first approach employed intensity-based segmentation of Dixon MRI for bulk-density assignment (sCTD). The second step added spine density information using an atlas of CT and Dixon MRI (sCTDS). The third iteration used a polynomial function relating Hounsfield units and normalised T1w image intensity to account for variable lung density (sCTDSL). Motion information in 4D-T1w MRI was applied to generate synthetic CT in midposition and in twenty respiratory phases. For six lung cancer patients, synthetic 4D-CT was validated against 4D-CT in midposition by comparison of Hounsfield units and dose-volume metrics. Dosimetric differences found by comparing sCTD,DS,DSL and CT were evaluated using a Wilcoxon signed-rank test (p = 0.05). Compared to sCTD and sCTDS, planning on sCTDSL significantly reduced absolute dosimetric differences in the planning target volume metrics to less than 98 cGy (1.7% of the prescribed dose) on average. When comparing sCTDSL and CT, average radiodensity differences were within 97 Hounsfield units and dosimetric differences were significant only for the planning target volume D99% metric. All methods produced clinically acceptable results for the organs at risk in accordance with the UK SABR consensus guidelines and the LungTech EORTC phase II trial. The overall good agreement between sCTDSL and CT demonstrates the feasibility of employing synthetic 4D-CT for plan adaptation on hybrid MR-guided radiotherapy systems.

Significance: The effects of varying the indocyanine green injection dose, injection rate, physiologic dispersion of dye, and intravenous tubing volume propagate into the shape and magnitude of the arterial input function (AIF) during intraoperative fluorescence perfusion assessment, thereby altering the observed kinetics of the fluorescence images in vivo. Aim: Numerical simulations are used to demonstrate the effect of AIF on metrics derived from tissue concentration curves such as peak fluorescence, time-to-peak (TTP), and egress slope. Approach: Forward models of tissue concentration were produced by convolving simulated AIFs with the adiabatic approximation to the tissue homogeneity model using input parameters representing six different tissue examples (normal brain, glioma, normal skin, ischemic skin, normal bone, and osteonecrosis). Results: The results show that AIF perturbations result in variations in estimates of total intensity of up to 80% and TTP error of up to 200%, with the errors more dominant in brain, less in skin, and less in bone. Interestingly, error in ingress slope was as high as 60% across all tissue types. These are key observable parameters used in fluorescence imaging either implicitly by viewing the image or explicitly through intensity fitting algorithms. Correcting by deconvolving the image with a measured subject-specific AIF provides an intuitive means of visualizing the data while also removing the source of variance and allowing intra- and intersubject comparisons. Conclusions: These results suggest that intraoperative fluorescence perfusion assessment should be corrected by patient-specific AIFs measured by pulse dye densitometry.

2D cine MR imaging may be utilized to monitor rapidly moving tumors and organs-at-risk for real-time adaptive radiotherapy. This study systematically investigates the impact of geometric imaging parameters on the ability of 2D cine MR imaging to guide template-matching-driven autocontouring of lung tumors and abdominal organs. Abdominal 4D MR images were acquired of six healthy volunteers and thoracic 4D MR images were obtained of eight lung cancer patients. At each breathing phase of the images, the left kidney and gallbladder or lung tumor, respectively, were outlined as volumes of interest. These images and contours were used to create artificial 2D cine MR images, while simultaneously serving as 3D ground truth. We explored the impact of five different imaging parameters (pixel size, slice thickness, imaging plane orientation, number and relative alignment of images as well as strategies to create training images). For each possible combination of imaging parameters, we generated artificial 2D cine MR images as training and test images. A template-matching algorithm used the training images to determine the tumor or organ position in the test images. Subsequently, a 3D base contour was shifted to the determined position and compared to the ground truth via centroid distance and Dice similarity coefficient. The median centroid distance between adapted and ground truth contours was 1.56 mm for the kidney, 3.81 mm for the gallbladder and 1.03 mm for the lung tumor (median Dice similarity coefficient: 0.95, 0.72 and 0.93). We observed that a decrease in image resolution led to a modest decrease in localization accuracy, especially for the small gallbladder. However, for all volumes of interest localization accuracy varied substantially more between subjects than due to the different imaging parameters. Automated tumor and organ localization using 2D cine MR imaging and template-matching-based autocontouring is robust against variation of geometric imaging parameters. Future work and optimization efforts of 2D cine MR imaging for real-time adaptive radiotherapy is needed to characterize the influence of sequence- and anatomical site-specific imaging contrast.

BackgroundThe relationship between cortical thickness (CThick) and sulcal depth (SDepth) changes across brain regions during development. Epilepsy youth have CThick and SDepth abnormalities and prevalent psychiatric disorders.AimsThis study compared the CThick–SDepth relationship in children with focal epilepsy with typically developing children (TDC) and the role played by seizure and psychopathology variables.MethodA surface-based, computational high-resolution three-dimesional (3D) magnetic resonance image analytic technique compared regional CThick–SDepth relationships in 42 participants with focal epilepsy and 46 TDC (6–16 years) imaged in a 1.5 Tesla scanner. Psychiatric interviews administered to each participant yielded psychiatric diagnoses. Parents provided seizure-related information.ResultsThe TDC group alone demonstrated a significant negative medial fronto-orbital CThick–SDepth correlation. Focal epilepsy participants with but not without psychiatric diagnoses showed significant positive pre-central and post-central CThick–SDepth associations not found in TDC. Although the history of prolonged seizures was significantly associated with the postcentral CThick–SDepth correlation, it was unrelated to the presence/absence of psychiatric diagnoses.ConclusionsAbnormal CThick–SDepth pre-central and post-central associations might be a psychopathology biomarker in paediatric focal epilepsy.

The Challenge on Liver Ultrasound Tracking (CLUST) was held in conjunction with the MICCAI 2014 conference to enable direct comparison of tracking methods for this application. This paper reports the outcome of this challenge, including setup, methods, results and experiences. The database included 54 2D and 3D sequences of the liver of healthy volunteers and tumor patients under free breathing. Participants had to provide the tracking results of 90% of the data (test set) for pre-defined point-landmarks (healthy volunteers) or for tumor segmentations (patient data). In this paper we compare the best six methods which participated in the challenge. Quantitative evaluation was performed by the organizers with respect to manual annotations. Results of all methods showed a mean tracking error ranging between 1.4 mm and 2.1 mm for 2D points, and between 2.6 mm and 4.6 mm for 3D points. Fusing all automatic results by considering the median tracking results, improved the mean error to 1.2 mm (2D) and 2.5 mm (3D). For all methods, the performance is still not comparable to human inter-rater variability, with a mean tracking error of 0.5-0.6 mm (2D) and 1.2-1.8 mm (3D). The segmentation task was fulfilled only by one participant, resulting in a Dice coefficient ranging from 76.7% to 92.3%. The CLUST database continues to be available and the online leader-board will be updated as an ongoing challenge.

Functional connectivity is the statistical association of neuronal activity time courses across distinct brain regions, supporting specific cognitive processes. This coordination of activity is likely to be highly important for complex aspects of cognition, such as the communication of fluctuating task goals from higher‐order control regions to lower‐order, functionally specific regions. Some of these functional connections are identifiable even when relevant cognitive tasks are not being performed (i.e. at rest). We used magnetoencephalographic recordings projected into source space to demonstrate that resting state networks in childhood have electrophysiological underpinnings that are evident in the spontaneous fluctuations of oscillatory brain activity. Using the temporal structure of these oscillatory patterns we were able to identify a number of functional resting state networks analogous to those reported in the adult literature. In a second analysis we fused this dynamic temporal information with the spatial information from a functional magnetic resonance imaging analysis of functional connectivity, to demonstrate that inter‐subject variability in these electrophysiological measures of functional connectivity is correlated with individual differences in cognitive ability: the strength of connectivity between a fronto‐parietal network and lower‐level processing areas in inferior temporal cortex was associated with spatial working memory capacity, as measured outside the scanner with educationally relevant standardized assessments. This study represents the first exploration of the electrophysiological mechanisms underpinning resting state functional connectivity in source space in childhood, and the extent to which the strength of particular connections is associated with cognitive ability.

Children who experience severe early life stress show persistent deficits in many aspects of cognitive and social adaptation. Early stress might be associated with these broad changes in functioning because it impairs general learning mechanisms. To explore this possibility, we examined whether individuals who experienced abusive caregiving in childhood had difficulties with instrumental learning and/or cognitive flexibility as adolescents. Fifty‐three 14–17‐year‐old adolescents (31 exposed to high levels of childhood stress, 22 control) completed an fMRI task that required them to first learn associations in the environment and then update those pairings. Adolescents with histories of early life stress eventually learned to pair stimuli with both positive and negative outcomes, but did so more slowly than their peers. Furthermore, these stress‐exposed adolescents showed markedly impaired cognitive flexibility; they were less able than their peers to update those pairings when the contingencies changed. These learning problems were reflected in abnormal activity in learning‐ and attention‐related brain circuitry. Both altered patterns of learning and neural activation were associated with the severity of lifetime stress that the adolescents had experienced. Taken together, the results of this experiment suggest that basic learning processes are impaired in adolescents exposed to early life stress. These general learning mechanisms may help explain the emergence of social problems observed in these individuals.

© 2017 The Authors. Developmental Science Published by John Wiley & Sons Ltd. Analogical reasoning, or the ability to find correspondences between entities based on shared relationships, supports knowledge acquisition. As such, the development of this ability during childhood is thought to promote learning. Here, we sought to better understand the mechanisms by which analogical reasoning about semantic relations improves over childhood and adolescence (e.g. chalk is to chalkboard as pen is to…?). We hypothesized that age-related differences would manifest as differences in the brain regions associated with one or more of the following cognitive functions: (1) controlled semantic retrieval, or the ability to retrieve task-relevant semantic associations; (2) response control, or the ability to override the tendency to respond to a salient distractor; and/or (3) relational integration, or the ability to consider jointly two mental relations. In order to test these hypotheses, we analyzed patterns of fMRI activation during performance of a pictorial propositional analogy task across 95 typically developing children between the ages of 6 and 18 years old. Despite large age-related differences in task performance, particularly over ages 6–10 but through to around age 14, participants across the whole age range recruited a common network of frontal, parietal and temporal regions. However, activation in a brain region that has been implicated in controlled semantic retrieval – left anterior prefrontal cortex (BA 47/45) – was positively correlated with age, and also with performance after controlling for age. This finding indicates that improved performance over middle childhood and early adolescence on this analogical reasoning task is driven largely by improvements in the ability to selectively retrieve task-relevant semantic relationships.

Liver dynamic contrast enhanced (DCE) MRI pharmacokinetic modelling could be useful in the assessment of diffuse liver disease and focal liver lesions, but is compromised by errors in arterial input function (AIF) sampling. In this study, we apply cardiac output correction to arterial input functions (AIFs) for liver DCE MRI and investigate the effect on dual-input single compartment hepatic perfusion parameter estimation and reproducibility. Thirteen healthy volunteers (28.7 ± 1.94 years, seven males) underwent liver DCE MRI and cardiac output measurement using aortic root phase contrast MRI (PCMRI), with reproducibility (n = 9) measured at 7 d. Cardiac output AIF correction was undertaken by constraining the first pass AIF enhancement curve using the indicator-dilution principle. Hepatic perfusion parameters with and without cardiac output AIF correction were compared and 7 d reproducibility assessed. Differences between cardiac output corrected and uncorrected liver DCE MRI portal venous (PV) perfusion (p = 0.066), total liver blood flow (TLBF) (p = 0.101), hepatic arterial (HA) fraction (p = 0.895), mean transit time (MTT) (p = 0.646), distribution volume (DV) (p = 0.890) were not significantly different. Seven day corrected HA fraction reproducibility was improved (mean difference 0.3%, Bland–Altman 95% limits-of-agreement (BA95%LoA) ±27.9%, coefficient of variation (CoV) 61.4% versus 9.3%, ±35.5%, 81.7% respectively without correction). Seven day uncorrected PV perfusion was also improved (mean difference 9.3 ml min−1/100 g, BA95%LoA ±506.1 ml min−1/100 g, CoV 64.1% versus 0.9 ml min−1/100 g, ±562.8 ml min−1/100 g, 65.1% respectively with correction) as was uncorrected TLBF (mean difference 43.8 ml min−1/100 g, BA95%LoA ±586.7 ml min−1/ 100 g, CoV 58.3% versus 13.3 ml min−1/100 g, ±661.5 ml min−1/100 g, 60.9% respectively with correction). Reproducibility of uncorrected MTT was similar (uncorrected mean difference 2.4 s, BA95%LoA ±26.7 s, CoV 60.8% uncorrected versus 3.7 s, ±27.8 s, 62.0% respectively with correction), as was and DV (uncorrected mean difference 14.1%, BA95%LoA ±48.2%, CoV 24.7% versus 10.3%, ±46.0%, 23.9% respectively with correction). Cardiac output AIF correction does not significantly affect the estimation of hepatic perfusion parameters but demonstrates improvements in normal volunteer 7 d HA fraction reproducibility, but deterioration in PV perfusion and TLBF reproducibility. Improved HA fraction reproducibility maybe important as arterialisation of liver perfusion is increased in chronic liver disease and within malignant liver lesions.

Physiological fluctuations are expected to be a dominant source of noise in blood oxygenation level-dependent (BOLD) magnetic resonance imaging (MRI) experiments to assess tumour oxygenation and angiogenesis. This work investigates the impact of various physiological noise regressors: retrospective image correction (RETROICOR), heart rate (HR) and respiratory volume per unit time (RVT), on signal variance and the detection of BOLD contrast in the breast in response to a modulated respiratory stimulus. BOLD MRI was performed at 3 T in ten volunteers at rest and during cycles of oxygen and carbogen gas breathing. RETROICOR was optimized using F-tests to determine which cardiac and respiratory phase terms accounted for a significant amount of signal variance. A nested regression analysis was performed to assess the effect of RETROICOR, HR and RVT on the model fit residuals, temporal signal-to-noise ratio, and BOLD activation parameters. The optimized RETROICOR model accounted for the largest amount of signal variance (\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{upgreek} \usepackage{mathrsfs} \setlength{\oddsidemargin}{-69pt} \begin{document} }{}$ \Delta R_{\text{adj}}^{2}$ \end{document}ΔRadj2 = 3.3 ± 2.1%) and improved the detection of BOLD activation (P = 0.002). Inclusion of HR and RVT regressors explained additional signal variance, but had a negative impact on activation parameter estimation (P

Cerebral edema is a severe complication of ischemic cerebrovascular disease, which can lead to microcirculation compression resulting in additional ischemic damage. Real-time and continuous in vivo imaging techniques for edema detection are of great significance to basic research on cerebral edema. We attempted to monitor the cerebral edema status in rats with middle cerebral artery occlusion (MCAO) over time, using a wide field-of-view swept-source optical coherence tomography (SS-OCT) system. Optical attenuation coefficients (OACs) were calculated by an optimized depth-resolved estimation method, and en face OAC maps covering the whole cortex were obtained. Then, the tissue affected by edema was segmented from the OAC maps, and the cortical area affected by edema was estimated. Both magnetic resonance image (MRI) and brain water content measurements were used to verify the presence of cerebral edema. The results showed that the average OAC of the ischemic area gradually decreased as cerebral edema progressed, and the edema area detected by SS-OCT had high similarity in position and shape to that obtained by MRI. This work extends the application of OCT and provides an option for detecting cerebral edema in vivo after ischemic stroke.

Age-related hippocampal formation (HF) atrophy has been documented on MRI studies using volumetric analysis and visual rating scales. This retrospective cross-sectional study aimed to compare linear MRI measurements of the HF between young (1–3 years) and old (>10 years) non-brachycephalic dogs, with normal brain anatomy and cerebrospinal fluid (CSF) analysis. Right and left hippocampal formation height (HFH), height of the brain (HB) and mean HFH/HB ratio were measured by two observers on a transverse T2 fluid-attenuated inversion recovery sequence containing rostral colliculi and mesencephalic aqueduct.119 MRI studies were enrolled: 75 young and 44 old dogs. Left and right HFH were greater (p

The objective of our study is to develop a multimodality approach by combining magnetic resonance imaging (MRI) and optical imaging methods to assess acute murine colitis at the macro- and microscopic level. In vivo MRI is used to measure the cross-sectional areas of colons at the macroscopic level. Dual-color confocal laser endomicroscopy (CLE) allows in vivo examination of the fluorescently labeled epithelial cells and microvessels in the mucosa with a spatial resolution of ∼1.4 μm during ongoing endoscopy. To further validate the structural changes of the colons in three-dimensions, ex vivo light-sheet fluorescence microscopy (LSFM) is applied for in-toto imaging of cleared colon sections. MRI, LSFM, and CLE findings are significantly correlated with histological scoring (p

Diffuse optical tomography has demonstrated significant potential for clinical utility in the diagnosis and prognosis of breast cancer, and its use in combination with other structural imaging modalities improves lesion localization and the quantification of functional tissue properties. Here, we introduce a hybrid diffuse optical imaging system that operates concurrently with magnetic resonance imaging (MRI) in the imaging suite, utilizing commercially available MR surface coils. The instrument acquires both continuous-wave and time-domain diffuse optical data in the parallel-plate geometry, permitting both absolute assignment of tissue optical properties and three-dimensional tomography; moreover, the instrument is designed to incorporate diffuse correlation spectroscopic measurements for probing tissue blood flow. The instrument is described in detail here. Image reconstructions of a tissue phantom are presented as an initial indicator of the system’s ability to accurately reconstruct optical properties and the concrete benefits of the spatial constraints provided by concurrent MRI. Last, we briefly discuss how various data combinations that the instrument could facilitate, including tissue perfusion, can enable more comprehensive assessment of lesion physiology.

Delays between contrast agent (CA) arrival at the site of vascular input function (VIF) sampling and the tissue of interest affect dynamic contrast enhanced (DCE) MRI pharmacokinetic modelling. We investigate effects of altering VIF CA bolus arrival delays on liver DCE MRI perfusion parameters, propose an alternative approach to estimating delays and evaluate reproducibility. Thirteen healthy volunteers (28.7 ± 1.9 years, seven males) underwent liver DCE MRI using dual-input single compartment modelling, with reproducibility (n = 9) measured at 7 days. Effects of VIF CA bolus arrival delays were assessed for arterial and portal venous input functions. Delays were pre-estimated using linear regression, with restricted free modelling around the pre-estimated delay. Perfusion parameters and 7 days reproducibility were compared using this method, freely modelled delays and no delays using one-way ANOVA. Reproducibility was assessed using Bland–Altman analysis of agreement. Maximum percent change relative to parameters obtained using zero delays, were −31% for portal venous (PV) perfusion, +43% for total liver blood flow (TLBF), +3247% for hepatic arterial (HA) fraction, +150% for mean transit time and −10% for distribution volume. Differences were demonstrated between the 3 methods for PV perfusion (p = 0.0085) and HA fraction (p

Physics in medicine and biology 61(9), 3500-3526 (2016). doi:10.1088/0031-9155/61/9/3500, Published by IOP Publ., Bristol

Hyperion-IID is a positron emission tomography (PET) insert which allows simultaneous operation in a clinical magnetic resonance imaging (MRI) scanner. To read out the scintillation light of the employed LYSO crystal arrays with a pitch of 1 mm pitch and 12 mm in height, digital silicon photomultipliers (DPC 3200-22, Philips Digital Photon Counting) (DPC) are used. The basic PET performance in terms of energy resolution, coincidence resolution time (CRT) and sensitivity as a function of operating parameters, such as the operating temperature, the applied overvoltage, activity and configuration parameters of the DPCs, were evaluated on system level. The measured energy resolution did not show a large dependency on the selected parameters and is in the range of 12.4-12.9% for low activities and degrades to ~13.6% at activities of ~100 MBq. The CRT strongly depends on the selected trigger scheme (trig) of the DPCs. We measured approximately 260 ps, 440 ps, 540 ps and 1300 ps for trig 1-4, respectively. The trues sensitivity for a NEMA NU 4 mouse-sized scatter phantom with a 70-mm-long tube of activity was dependent on the operating parameters and was determined to be 0.4-1.4% at low activities. The random fraction stayed below 5% at activities up to 100 MBq and the scatter fraction was evaluated as ~6% for an energy window of 411-561 keV and ~16% for 250-625 keV. Furthermore, we performed imaging experiments using a mouse-sized hot-rod phantom and a large rabbit-sized phantom. In 2D slices of the reconstructed mouse-sized hot-rod phantom ({\O} = 28 mm), the rods were distinguishable from each other down to a rod size of 0.8 mm. There was no benefit of the better CRT of trig 1 over trig 3, where in the larger rabbit-sized phantom ({\O} = 114 mm), we could show a clear improvement of image quality using the time-of-flight information., Comment: Final journal version including the supplemntal data. The images in the supplement were compressed to meet the arXiv file size limit

MRI of the penis is an expensive test that is not always superior to clinical examination or ultrasound. However, it shows many of the important structures, and in particular the combination of tumescence from intracavernosal alprostadil, and high-resolution T(2) sequences show the glans, corpora and the tunica albuginea well. In this paper we summarise the radiological anatomy and discuss the indications for MRI. For penile cancer, it may be useful in cases where the local stage is not apparent clinically. In priapism, it is an emerging technique for assessing corporal viability, and in fracture it can in most cases make the diagnosis and locate the injury. In some cases of penile fibrosis and Peyronie's disease, it may aid surgical planning, and in complex pelvic fracture may replace or augment conventional urethrography. It is an excellent investigation for the malfunctioning penile prosthesis.

Background and purpose: Age related white matter changes (ARWMC) are frequent in non-demented old subjects and are associated with impaired cognitive function. Our aim was to study the influence of vascular risk factors and ARWMC on the neuropsychological performance of an independent elderly population, to see if vascular risk factors impair cognition in addition to the effects of ARWMC. Methods: Independent subjects, aged 65-84 years, with any degree of ARWMC were assessed using a comprehensive neuropsychological battery including the Mini-Mental State Examination (MMSE), VADAS-Cog (Alzheimer's disease assessment scale) and the Stroop and Trail Making test. Vascular risk factors were recorded and ARWMC (measured by MRI) were graded into three classes. The impact of vascular risk factors and ARWMC on neuropsychological performance was assessed by linear regression analyses, with adjustment for age and education. Results: 638 patients (74.1 (5) years old, 55% women) were included. Patients with severe ARWMC performed significantly worse on global tests of cognition, executive functions, speed and motor control, attention, naming and visuoconstructional praxis. Diabetes interfered with tests of executive function, attention, speed and motor control, memory and naming. Arterial hypertension and stroke influenced executive functions and attention. The effect of these vascular risk factors was independent of the severity of ARWMC, age and education. Conclusion: ARWMC is related to worse performance in executive function, attention and speed. Diabetes, hypertension and previous stroke influenced neuropsychological performance, independently of the severity of ARWMC, stressing the need to control vascular risk factors in order to prevent cognitive decline in the elderly.

Objective: To estimate the frequency, mechanisms and predictive factors of sleep apnoea syndrome (SAS) in a large group of children and adults with type I (CMI) and II (CMII) Chiari malformation (CM). Background: The anatomical and functional integrity of both respiratory circuits and lower cranial nerves controlling the upper airway is necessary for breathing control during sleep. These latter structures may be altered in CM, and a few investigations have reported CM related sleep disordered breathing. Methods: Forty-six consecutive unrelated patients with CM (40 CMI, six CMII), of which 20 were children (eight males) and 26 were adults (12 males), underwent physical, neurological and oto-rhino-laryngoscopic examination, MRI and polysomnography. Results: SAS was present in 31 (67.4%) of the patients with CM (70% of CMI, 50% of CMII, including mainly children). Sixty per cent of children with CM exhibited SAS, including 35% with obstructive (OSAS) and 25% with central (CSAS) sleep apnoea syndrome. SAS was observed in 73% of CM adults (57.7% OSAS, 15.4% CSAS). Severe SAS was found in 23% of CM adults. Multiple regression analysis revealed that age, type II Chiari and vocal cord paralysis predicted the central apnoea index. Conclusion: SAS is highly prevalent in all age groups of patients suffering from CM. CSAS, a rare condition in the general population, was common among the patients with CM in our study. Sleep disordered breathing associated with CM may explain the high frequency of respiratory failures observed during curative surgery of CM. Our results suggest that SAS should be systematically screened for in patients with CM, especially before surgery.

To determine the effect of electrode contact location on efficacy of bilateral globus pallidus internus (GPi) deep brain stimulation (DBS) for primary generalised dystonia (PGD).A consecutive series of 15 patients with PGD (10 females, mean age 42 years, seven DYT1) who underwent bilateral GPi DBS, were assessed using the Burke-Fahn-Marsden (BFM) dystonia scale before and 6 months after surgery. The position of the stimulated electrode contact(s) was determined from the postoperative stereotactic MRI. Contralateral limb and total axial BFM subscores were compared with the location of the stimulated contact(s) within the GPi.The mean total BFM score decreased from 38.9 preoperatively to 11.9 at 6 months, an improvement of 69.5% (p0.00001). Cluster analysis of the stimulated contact coordinates identified two groups, distributed along an anterodorsal to posteroventral axis. Clinical improvement was greater for posteroventral than anterodorsal stimulation for the arm (86% vs 52%; p0.05) and trunk (96% vs 65%; p0.05) and inversely correlated with the y coordinate. For the leg, posteroventral and anterodorsal stimulation were of equivalent efficacy. Overall clinical improvement was maximal with posteroventral stimulation (89% vs 67%; p0.05) and inversely correlated with the y (A-P) coordinate (r = -0.62, p0.05).GPi DBS is effective for PGD but outcome is dependent on contact location. Posteroventral GPi stimulation provides the best overall effect and is superior for the arm and trunk. These results may be explained by the functional anatomy of GPi and its outflow tracts.

Background: Inflammation is a recognised risk factor for the vulnerable atherosclerotic plaque. The aim of this study was to explore whether there is a difference in the degree of magnetic resonance (MR) defined inflammation using ultra small superparamagnetic iron oxide (USPIO) particles within carotid atheroma in completely asymptomatic individuals and the asymptomatic carotid stenosis contralateral to the symptomatic side. Methods: 20 symptomatic patients with contralateral disease and 20 completely asymptomatic patients underwent multi-sequence MR imaging before and 36 h after USPIO infusion. Images were manually segmented into quadrants and signal change in each quadrant was calculated following USPIO administration. Mean signal change was compared across all quadrants in the two groups. Results: The mean percentage of quadrants showing signal loss was 53% in the contralateral group compared with 31% in completely asymptomatic individuals (p = 0.025). The mean percentages showing enhancement were 44% and 65%, respectively (p = 0.024). The mean signal difference between the two groups was 8.6% (95% CI 1.6% to 15.6%; p = 0.017). Conclusions: Truly asymptomatic plaques seem to demonstrate inflammation but not to the extent of the contralateral asymptomatic stenosis to the symptomatic side. Inflammatory activity may be a significant risk factor in asymptomatic disease.

Background: Clinical assessment of cerebral concussion relies on the presence and duration of post concussive symptoms (PCS). Given that these PCS are subjective reports and not always specific to concussion, their usefulness remains to be validated. Objective: To evaluate the usefulness of self-reported PCS by means of cognitive tests and functional MRI (fMRI). Method: 28 male athletes with and without concussion were grouped according to their PCS score. They were then administered a computerised cognitive test battery and submitted to an fMRI session where cerebral activations associated with verbal and non-verbal working memory tasks were analysed. Results: Behaviourally, response accuracy and speed on the cognitive test battery were comparable for the control and low PCS group. The moderate PCS group showed significantly slower response times than the control group on the matching (p

Objective: X linked spinobulbar muscular atrophy (Kennedy disease (KD)), which is clinically characterised mainly by neuromuscular and endocrine symptoms, has to be considered as a multisystem disorder. Based on clinical evidence of central nervous system involvement, potential KD associated cerebral volume alterations were analysed in vivo. Methods: Whole brain based analysis of optimised voxel based morphometry (VBM) was applied to three dimensional MRI data from 18 genetically confirmed KD patients and compared with age matched controls. Results: Subtle decreases in grey matter volume, mainly localised in frontal areas, were found, but extensive white matter atrophy was observed, particularly in frontal areas, but also involving multiple additional subcortical areas, the cerebellar white matter and the dorsal brainstem from the midbrain to the medulla oblongata. Conclusion: The VBM results demonstrated a morphological correlate of central nervous system involvement in KD, in agreement with aspects of the clinical phenotype (behavioural abnormalities, central–peripheral axonopathy) and with pathohistological findings.

Background: Neurofibromatosis type 1 (NF1) is a single gene disorder associated with a high frequency of cognitive deficits and a complex cognitive phenotype. These cognitive deficits have been associated with focal areas of high signal intensity on T2 weighted MRI images but the relationship remains controversial. Method: A cohort of 76 children with NF1 and 45 unaffected sibling controls (aged 8–16 years) underwent extensive neuropsychological assessment, with the NF1 children having MRI examinations. Results: The presence or number of T2 hyperintensities (T2H) was not associated with cognitive dysfunction. However, the location of discrete (well circumscribed) T2H in the thalamus was associated with severe and generalised cognitive impairment. More diffuse lesions in the thalamus were also associated with reductions in IQ but the effects were less marked compared with the discrete lesions. Comparing children with NF1 to their unaffected siblings revealed more subtle effects of the lesions on cognitive ability. Conclusions: T2H cannot be used in general as a radiological marker for cognitive deficits in children with NF1; however, lesions in the thalamus are strongly associated with cognitive impairment. It is possible that lesions in the thalamus in conjunction with more general thalamic hypometabolism may compound the level of thalamic dysfunction, resulting in cognitive deficits well beyond those produced by T2H in other regions.

Background: Studies of long term outcome after epilepsy surgery for cortical malformations are rare. In this study, we report our experience with surgical treatment and year to year long term outcome for a subgroup of patients with focal cortical dysplasia (FCD). Methods: We retrospectively analysed the records of 49 patients (females n = 26; males n = 23; mean age 25 (11) years) with a mean duration of epilepsy of 18 years (range 1–45). Preoperative MRI, histological results based on the Palmini classification and clinical year to year follow-up according to the International League Against Epilepsy (ILAE) classification were available in all patients. Results: 98% of patients had a lesion on preoperative MRI. In addition to lobectomy (n = 9) or lesionectomy (n = 40), 14 patients had multiple subpial transections of the eloquent cortex. The resected tissue was classified as FCD type II b in 41 cases with an extratemporal (88%) and FCD type II a in 8 cases with a temporal localisation (100%). After a mean follow-up of 8.1 (4.5) years, 37 patients (76%) were seizure free, a subgroup of 23 patients (47%) had been completely seizure free since surgery (ILAE class 1a) and 4 patients (8%) had only auras (ILAE class 2). Over a 10 year follow-up, the proportion of satisfactory outcomes decreased, mainly within the first 3 years. During long term follow-up, 48% stopped antiepileptic drug treatment, 34% received a driver’s license and 57% found a job or training. Conclusion: Surgical treatment of epilepsy with FCD is not only successful in the short term but also has a satisfying long term outcome which remains constant after 3 years of follow-up but is not associated with better employment status or improvement in daily living.