The accurate measurement of three-dimensional (3D) fiber orientation in the brain is crucial for reconstructing fiber pathways and studying their involvement in neurological diseases. Comprehensive reconstruction of axonal tracts and small fascicles requires high-resolution technology beyond the ability of current in vivo imaging (e.g. diffusion magnetic resonance imaging). Optical imaging methods such as polarization-sensitive optical coherence tomography (PS-OCT) and polarization microscopy can quantify fiber orientation at micrometer resolution but have been limited to two-dimensional in-plane orientation or thin slices, preventing the comprehensive study of connectivity in 3D. In this work we present a novel method to quantify volumetric 3D orientation in full angular space with PS-OCT. We measure the polarization contrasts of the brain sample from two illumination angles of 0 and 15 degrees and apply a computational method that yields the 3D optic axis orientation and true birefringence. We further present 3D fiber orientation maps of entire coronal cerebrum sections and brainstem with 10 μm in-plane resolution, revealing unprecedented details of fiber configurations. We envision that our method will open a promising avenue towards large-scale 3D fiber axis mapping in the human brain as well as other complex fibrous tissues at microscopic level.

The accurate measurement of three-dimensional (3D) fiber orientation in the brain is crucial for reconstructing fiber pathways and studying their involvement in neurological diseases. Optical imaging methods such as polarization-sensitive optical coherence tomography (PS-OCT) provide important tools to directly quantify fiber orientation at micrometer resolution. However, brain imaging based on the optic axis by PS-OCT so far has been limited to two-dimensional in-plane orientation, preventing the comprehensive study of connectivity in 3D. In this work, we present a novel method to obtain the 3D fiber orientation in full angular space with only two illumination angles. We measure the optic axis orientation and the apparent birefringence by PS-OCT from a normal and a 15 deg tilted illumination, and then apply a computational method yielding the 3D optic axis orientation and true birefringence. We verify that our method accurately recovers a large range of through-plane orientations from -85 deg to 85 deg with a high angular precision. We further present 3D fiber orientation maps of entire coronal sections of human cerebrum and brainstem with 10 μm in-plane resolution, revealing unprecedented details of fiber configurations. We envision that further development of our method will open a promising avenue towards large-scale 3D fiber axis mapping in the human brain and other complex fibrous tissues at microscopic level.

AbstractIntroductionVisual assessment and imaging of the donor liver are inaccurate in predicting fibrosis and remain surrogates for histopathology. We demonstrate that 3‐s scans using a handheld near‐infrared‐spectroscopy (NIRS) instrument can identify and quantify fibrosis in fresh human liver samples.MethodsWe undertook NIRS scans on 107 samples from 27 patients, 88 from 23 patients with liver disease, and 19 from four organ donors.ResultsLiver disease patients had a median immature fibrosis of 40% (interquartile range [IQR] 20–60) and mature fibrosis of 30% (10%–50%) on histopathology. The organ donor livers had a median fibrosis (both mature and immature) of 10% (IQR 5%–15%). Using machine learning, this study detected presence of cirrhosis and METAVIR grade of fibrosis with a classification accuracy of 96.3% and 97.2%, precision of 96.3% and 97.0%, recall of 96.3% and 97.2%, specificity of 95.4% and 98.0% and area under receiver operator curve of 0.977 and 0.999, respectively. Using partial‐least square regression machine learning, this study predicted the percentage of both immature (R2 = 0.842) and mature (R2 = 0.837) with a low margin of error (root mean square of error of 9.76% and 7.96%, respectively).ConclusionThis study demonstrates that a point‐of‐care NIRS instrument can accurately detect, quantify and classify liver fibrosis using machine learning.

Limitations in the accuracy of brain pathways reconstructed by diffusion MRI (dMRI) tractography have received considerable attention. While the technical advances spearheaded by the Human Connectome Project (HCP) led to significant improvements in dMRI data quality, it remains unclear how these data should be analyzed to maximize tractography accuracy. Over a period of two years, we have engaged the dMRI community in the IronTract Challenge, which aims to answer this question by leveraging a unique dataset. Macaque brains that have received both tracer injections and ex vivo dMRI at high spatial and angular resolution allow a comprehensive, quantitative assessment of tractography accuracy on state-of-the-art dMRI acquisition schemes. We find that, when analysis methods are carefully optimized, the HCP scheme can achieve similar accuracy as a more time-consuming, Cartesian-grid scheme. Importantly, we show that simple pre- and post-processing strategies can improve the accuracy and robustness of many tractography methods. Finally, we find that fiber configurations that go beyond crossing ( e . g ., fanning, branching) are the most challenging for tractography. The IronTract Challenge remains open and we hope that it can serve as a valuable validation tool for both users and developers of dMRI analysis methods.

Adolescents experiencing anxiety or depression exhibit cognitive biases favoring the processing of negative emotional information. It remains unknown whether common neurobiological processes underlie these biases across anxiety and depression. Here, brain imaging was acquired from typical, anxious, and depressed adolescents during an emotional-interference task. Functional connectivity patterns were assessed while adolescents were cued to attend to or ignore faces. Results revealed a shared dimension of anxious and depressive symptoms was associated with reduced changes in connectivity patterns between conditions in which adolescents needed to ignore or attend to fearful faces. These findings were exclusive to fearful faces and observed only for functional connections with a primary face-representation area (fusiform gyrus). Results suggested a failure to flexibly adapt communication patterns with sensory-representation areas in the presence of negative emotional information, which may reflect a common neurobiological mechanism explaining biases favoring such information shared among adolescent anxiety and depression.

Background. We aimed to facilitate the donation of tissue samples for research by establishing a centralized system integrated in the organ donation program for collection, storage, and distribution of samples (the Australian Donation and Transplantation Biobank [ADTB]). Methods. Feasibility of a research biobank integrated within the deceased organ and tissue donation program was assessed. DonateLife Victoria sought consent for ADTB donation after consent was received for organ donation for transplantation from the donor’s senior available next of kin. ADTB samples were collected during donation surgery and distributed fresh to researchers or stored for future research. The main outcome measures were ADTB donation rates, ADTB sample collection, ADTB sample use, and to identify ethical considerations. Results. Over 2 y, samples were collected for the ADTB from 69 donors (28% of 249 donors). Samples were obtained from the spleen (n = 59, 86%), colon (n = 57, 83%), ileum (n = 56, 82%), duodenum (n = 55, 80%), blood (n = 55, 80%), bone marrow (n = 55, 80%), skin (n = 54, 78%), mesenteric lymph nodes (n = 56, 81%), liver (n = 21, 30%), lung (n = 29, 42%), and lung-draining lymph node (n = 29, 42%). Heart (n = 20), breast (n = 1), and lower urinary tract (n = 1) samples were obtained in the second year. Five hundred fifty-six samples were used in 19 ethics-approved research projects spanning the fields of immunology, microbiology, oncology, anatomy, physiology, and surgery. Conclusions. The integration of routine deceased donation and transplantation activities with a coordinated system for retrieval and allocation of donor samples for use in a range of research projects is feasible and valuable.

Objectives Endemic human coronaviruses (hCoVs) circulate worldwide but cause minimal mortality. Although seroconversion to hCoV is near ubiquitous during childhood, little is known about hCoV-specific T-cell memory in adults. Methods We quantified CD4 T-cell and antibody responses to hCoV spike antigens in 42 SARS-CoV-2-uninfected individuals. Antigen-specific memory T cells and circulating T follicular helper (cTFH) cells were identified using an activation-induced marker assay and characterised for memory phenotype and chemokine receptor expression. Results T-cell responses were widespread within conventional memory and cTFH compartments but did not correlate with IgG titres. SARS-CoV-2 cross-reactive T cells were observed in 48% of participants and correlated with HKU1 memory. hCoV-specific T cells exhibited a CCR6(+) central memory phenotype in the blood, but were enriched for frequency and CXCR3 expression in human lung-draining lymph nodes. Conclusion Overall, hCoV-specific humoral and cellular memory are independently maintained, with a shared phenotype existing among coronavirus-specific CD4 T cells. This understanding of endemic coronavirus immunity provides insight into the homeostatic maintenance of immune responses that are likely to be critical components of protection against SARS-CoV-2.

The vascular network in the human brain is universally involved in physiology and neural activity and the alteration is commonly associated with neurological disorders such as traumatic brain injury, stroke, multiple sclerosis, and Alzheimer’s disease. However, small arterioles, venules, and the capillary networks are beyond the resolution of in vivo MRI and optical microscopy only reveals the vasculature of cortex in small animals. We reported a vascular network reconstruction with an automatic serial sectioning polarization sensitive optical coherence tomography at 3.5 micrometer resolution in ex vivo human brain tissue. Pathological patterns surrounding the vessel walls were revealed as well.

OBJECTIVE:Although depression and anxiety often have distinct etiologies, they frequently co-occur in adolescence. Recent initiatives have underscored the importance of developing new ways of classifying mental illness based on underlying neural dimensions that cut across traditional diagnostic boundaries. Accordingly, the aim of the study was to clarify reward-related neural circuitry that may characterize depressed-anxious youth. METHOD:The Boston Adolescent Neuroimaging of Depression and Anxiety Human Connectome Project tested group differences regarding subcortical volume and nucleus accumbens activation during an incentive processing task among 14- to 17-year-old adolescents presenting with a primary depressive and/or anxiety disorder (n = 129) or no lifetime history of mental disorders (n = 64). In addition, multimodal modeling examined predictors of depression and anxiety symptom change over a 6-month follow-up period. RESULTS:Our findings highlighted considerable convergence. Relative to healthy youth, depressed-anxious adolescents exhibited reduced nucleus accumbens volume and activation following reward receipt. These findings remained when removing all medicated participants (∼59% of depressed-anxious youth). Subgroup analyses comparing anxious-only, depressed-anxious, and healthy youth also were largely consistent. Multimodal modeling showed that only structural alterations predicted depressive symptoms over time. CONCLUSION:Multimodal findings highlight alterations within nucleus accumbens structure and function that characterize depressed-anxious adolescents. In the current hypothesis-driven analyses, however, only reduced nucleus accumbens volume predicted depressive symptoms over time. An important next step will be to clarify why structural alterations have an impact on reward-related processes and associated symptoms.

The importance of polarization-sensitive optical coherence tomography (PS-OCT) has been increasingly recognized in human brain imaging. Despite the recent progress of PS-OCT in revealing white matter architecture and orientation, quantification of fine-scale fiber tracts in the human brain cortex has been a challenging problem, due to a low birefringence in the gray matter. In this study, we investigated the effect of refractive index matching by 2,2'-thiodiethanol (TDE) immersion on the improvement of PS-OCT measurements in ex vivo human brain tissue. We show that we can obtain fiber orientation maps of U-fibers that underlie sulci, as well as cortical fibers in the gray matter, including radial fibers in gyri and distinct layers of fibers exhibiting laminar organization. Further analysis shows that index matching reduces the noise in axis orientation measurements by 56% and 39%, in white and gray matter, respectively. Index matching also enables precise measurements of apparent birefringence, which was underestimated in the white matter by 82% but overestimated in the gray matter by 16% prior to TDE immersion. Mathematical simulations show that the improvements are primarily attributed to the reduction in the tissue scattering coefficient, leading to an enhanced signal-to-noise ratio in deeper tissue regions, which could not be achieved by conventional noise reduction methods.

While many useful microstructural indices, as well as orientation distribution functions, can be obtained from multi-shell dMRI data, there is growing interest in exploring the richer set of microstructural features that can be extracted from the full ensemble average propagator (EAP). The EAP can be readily computed from diffusion spectrum imaging (DSI) data, at the cost of a very lengthy acquisition. Compressed sensing (CS) has been used to make DSI more practical by reducing its acquisition time. CS applied to DSI (CS-DSI) attempts to reconstruct the EAP from significantly undersampled q-space data. We present a post mortem validation study where we evaluate the ability of CS-DSI to approximate not only fully sampled DSI but also multi-shell acquisitions with high fidelity. Human brain samples are imaged with high-resolution DSI at 9.4T and with polarization-sensitive optical coherence tomography (PSOCT). The latter provides direct measurements of axonal orientations at microscopic resolutions, allowing us to evaluate the mesoscopic orientation estimates obtained from diffusion MRI, in terms of their angular error and the presence of spurious peaks. We test two fast, dictionary-based, L2-regularized algorithms for CS-DSI reconstruction. We find that, for a CS acceleration factor of R=3, i.e., an acquisition with 171 gradient directions, one of these methods is able to achieve both low angular error and low number of spurious peaks. With a scan length similar to that of high angular resolution multi-shell acquisition schemes, this CS-DSI approach is able to approximate both fully sampled DSI and multi-shell data with high accuracy. Thus it is suitable for orientation reconstruction and microstructural modeling techniques that require either grid- or shell-based acquisitions. We find that the signal-to-noise ratio (SNR) of the training data used to construct the dictionary can have an impact on the accuracy of CS-DSI, but that there is substantial robustness to loss of SNR in the test data. Finally, we show that, as the CS acceleration factor increases beyond R=3, the accuracy of these reconstruction methods degrade, either in terms of the angular error, or in terms of the number of spurious peaks. Our results provide useful benchmarks for the future development of even more efficient q-space acceleration techniques.

Objective To assess long term graft and patient survival after donor liver retransplantation in children in Australia and New Zealand during 1986-2017; to determine the factors that influence survival. Design Retrospective cohort analysis (registry data). Setting, participants Australia and New Zealand Liver Transplant Registry data for all liver retransplantations in children (under 18 years of age), 1986-2017, in all four paediatric and six adult liver transplantation centres in the two countries. Main outcome measures Graft and patient survival at one, 5, 10 and 15 years. Results 142 liver retransplantations were undertaken in children (59 during 1986-2000, 83 during 2001-2017). Kaplan-Meier survival analysis indicated that survival was significantly greater during 2001-2017 than 1986-2000 (P < 0.001). During 2001-2017, graft survival one year after retransplantation was 84%, at 5 years 75%, at 10 years 70%, and at 15 years 54%; patient survival was 89% at one year, 87% at 5 years, 87% at 10 years, and 71% at 15 years. Median time between transplantations was 0.2 years (IQR, 0.03-1.4 years) during 1986-2000, and 1.8 years (IQR, 0.1-6.8 years) during 2001-2017 (P = 0.002). The proportion of graft failures that involved split grafts was larger during 2001-2017 (35 of 83, 42%) than 1986-2000 (10 of 59, 17%). Graft type, cause of graft failure, and number of transplants did not influence survival following retransplantation. Conclusion Survival for children following retransplantation is excellent. Graft survival is similar for split and whole grafts. Children on the liver waiting list requiring retransplantation should have the same access to donor grafts as children requiring a first transplant.

The Connectomes Related to Human Diseases (CRHD) initiative was developed with the Human Connectome Project (HCP) to provide high-resolution, open-access, multi-modal MRI data to better understand the neural correlates of human disease. Here, we present an introduction to a CRHD project, the Boston Adolescent Neuroimaging of Depression and Anxiety (BANDA) study, which is collecting multimodal neuroimaging, clinical, and neuropsychological data from 225 adolescents (ages 14-17), 150 of whom are expected to have a diagnosis of depression and/or anxiety. Our transdiagnostic recruitment approach samples the full spectrum of depressed/anxious symptoms and their comorbidity, consistent with NIMH Research Domain Criteria (RDoC). We focused on an age range that is critical for brain development and for the onset of mental illness. This project sought to harmonize imaging sequences, hardware, and functional tasks with other HCP studies, although some changes were made to canonical HCP methods to accommodate our study population and questions. We present a thorough overview of our imaging sequences, hardware, and scanning protocol. We detail similarities and differences between this study and other HCP studies. We evaluate structural-, diffusion-, and functional-image-quality measures that may be influenced by clinical factors (e.g., disorder, symptomatology). Signal-to-noise and motion estimates from the first 140 adolescents suggest minimal influence of clinical factors on image quality. We anticipate enrollment of an additional 85 participants, most of whom are expected to have a diagnosis of anxiety and/or depression. Clinical and neuropsychological data from the first 140 participants are currently freely available through the National Institute of Mental Health Data Archive (NDA).

In the first study comparing high angular resolution diffusion MRI (dMRI) in the human brain to axonal orientation measurements from polarization-sensitive optical coherence tomography (PSOCT), we compare the accuracy of orientation estimates from various dMRI sampling schemes and reconstruction methods. We find that, if the reconstruction approach is chosen carefully, single-shell dMRI data can yield the same accuracy as multi-shell data, and only moderately lower accuracy than a full Cartesian-grid sampling scheme. Our results suggest that current dMRI reconstruction approaches do not benefit substantially from ultra-high b-values or from very large numbers of diffusion-encoding directions. We also show that accuracy remains stable across dMRI voxel sizes of 1 ​mm or smaller but degrades at 2 ​mm, particularly in areas of complex white-matter architecture. We also show that, as the spatial resolution is reduced, axonal configurations in a dMRI voxel can no longer be modeled as a small set of distinct axon populations, violating an assumption that is sometimes made by dMRI reconstruction techniques. Our findings have implications for in vivo studies and illustrate the value of PSOCT as a source of ground-truth measurements of white-matter organization that does not suffer from the distortions typical of histological techniques.

Background: Central hepatectomy (CH) is more difficult than extended hepatectomy (EH) and is associated with greater morbidity. In this modern era of liver management with aims to prevent post-hepatectomy liver failure (PHLF), there is a need to assess outcomes of CH as a parenchyma-sparing procedure for centrally located liver tumors. Methods: A total of 178 major liver resections performed by specialist surgeons from two Australian tertiary institutions between June 2009 and March 2017 were reviewed. Eleven patients had CH and 24 had EH over this study period. Indications and perioperative outcomes were compared between the groups. Results: The main indication for performing CH was colorectal liver metastases. There was no perioperative mortality in the CH group and four (16.7%) in the EH group (P=0.285). No group differences were found in median operative time [CH vs. EH: 450 min (290-840) vs. 523 min (310-860), P=0.328], intraoperative blood loss [850 mL (400-1500) vs. 650 mL (100-2000), P=0.746] or patients requiring intraoperative blood transfusion [1 (9.1%) vs. 7 (30.4%), P=0.227]. There was a trend towards fewer hepatectomy-specific complications in the CH group [3 (27.3%) vs. 13 (54.2%), P=0.167], including PHLF (CH vs. EH: 0 vs. 29.2%, P=0.072). Median length of stay was similar between groups [CH vs. EH: 9 days (5-23) vs. 12 days (4-85), P=0.244]. Conclusions: CH has equivalent postoperative outcomes to EH. There is a trend towards fewer hepatectomy-specific complications, including PHLF. In appropriate patients, CH may be considered as a safe parenchyma-sparing alternative to EH. (C) 2019 First Affiliated Hospital, Zhejiang University School of Medicine in China. Published by Elsevier B.V. All rights reserved.

BACKGROUND:Liver retransplantation is technically challenging, and historical outcomes are significantly worse than for first transplantations. This study aimed to assess graft and patient survival in all Australian and New Zealand liver transplantation units.METHODS:A retrospective cohort analysis was performed using data from the Australia and New Zealand Liver Transplant Registry. Graft and patient survival were analyzed according to era. Cox regression was used to determine recipient, donor, or intraoperative variables associated with outcomes.RESULTS:Between 1986 and 2017, Australia and New Zealand performed 4514 adult liver transplants, 302 (6.7%) of which were retransplantations (278 with 2, 22 with 3, 2 with 4). The main causes of graft failure were hepatic artery or portal vein thrombosis (29%), disease recurrence (21%), and graft nonfunction (15%). Patients retransplanted after 2000 had a graft survival of 85% at 1 year, 75% at 5 years, and 64% at 10 years. Patient survival was 89%, 81%, and 74%, respectively. This was higher than retransplantations before 2000 (P < 0.001). Univariate analysis found that increased recipient age (P = 0.001), recipient weight (P = 0.019), and donor age (P = 0.011) were associated with decreased graft survival prior to 2000; however, only increased patient weight was significant after 2000 (P = 0.041). Multivariate analysis found only increased recipient weight (P = 0.042) and donor age (P = 0.025) was significant prior to 2000. There was no difference in survival for second and third retransplants or comparing time to retransplant.CONCLUSIONS:Australia and New Zealand have excellent survival following liver retransplantation. These contemporary results should be utilized for transplant waitlist methods.

Evidence suggests that the renin angiotensin system (RAS) may play a role in the pathological splanchnic vasodilatation that leads to a hyperdynamic circulation in cirrhosis. An impaired contractile response to the angiotensin II peptide of the classical RAS system has been described in animal models of cirrhosis and in vivo in cirrhotic subjects. Furthermore, in experimental cirrhosis, the so-called alternate arm of the RAS was found to be upregulated and its effector peptide, angiotensin-(1-7) was shown to attenuate splanchnic vascular tone. The aim of this study was to explore the relevance of these findings to human disease. Omental arteries from cirrhotic and controls subjects were studied in isolation using a wire myograph. Varied protocols to evaluate the vasoactivity of RAS mediators were enacted. The contractile response to angiotensin II was comparable in cirrhotic vs control splanchnic arteries (61 +/- 9 vs 68 +/- 11% KPSS, respectively). Despite this, however, arterial contractility of the cirrhotic vessels correlated negatively with Child Pugh score (p = 0.0003, r = -0.83) and there was evidence that angiotensin II-induced contractility was increased in early cirrhosis. Angiotensin II-induced contractility was attenuated by angiotensin(1-7) in cirrhotic and control arteries, however, adrenergic responses were not affected by angiotensin-(1-7). Contractile responses to angiotensin II are preserved in narrow lumen human cirrhotic splanchnic arteries and are comparatively augmented in early disease. Angiotensin-(1-7) had no vasodilatory effect on adrenergic tone, however, attenuated angiotensin II-induced contractility, possibly through an Ang-(1-7)-AT1R interaction, and thus may contribute to pathological vasodilatation in human cirrhosis.