Maximizing SNR per unit time in diffusion MRI with multiband T-Hex spirals.

PURPOSE: The characterization of tissue microstructure using diffusion MRI (dMRI) signals is rapidly evolving, with increasing sophistication of signal representations and microstructure models. However, this progress often requires signals to be acquired with very high b-values (e.g., b > 30 ms/µm2 ), along many directions, and using multiple b-values, leading to long scan times and extremely low SNR in dMRI images. The purpose of this work is to boost the SNR efficiency of dMRI by combining three particularly efficient spatial encoding techniques and utilizing a high-performance gradient system (Gmax ≤ 300 mT/m) for efficient diffusion encoding. METHODS: Spiral readouts, multiband imaging, and sampling on tilted hexagonal grids (T-Hex) are combined and implemented on a 3T MRI system with ultra-strong gradients. Image reconstruction is performed through an iterative cg-SENSE algorithm incorporating static off-resonance distributions and field dynamics as measured with an NMR field camera. Additionally, T-Hex multiband is combined with a more conventional EPI-readout and compared with state-of-the-art blipped-CAIPIRINHA sampling. The advantage of the proposed approach is furthermore investigated for clinically available gradient performance and diffusion kurtosis imaging. RESULTS: High fidelity in vivo images with b-values up to 40 ms/µm2 are obtained. The approach provides superior SNR efficiency over other state-of-the-art multiband diffusion readout schemes. CONCLUSION: The demonstrated gains hold promise for the widespread dissemination of advanced microstructural scans, especially in clinical populations.

Giving the prostate the boost it needs: Spiral diffusion MRI using a high-performance whole-body gradient system for high b-values at short echo times.

PURPOSE: To address key issues of low SNR and image distortions in prostate diffusion MRI (dMRI) by means of using strong gradients, single-shot spiral readouts and an expanded encoding model for image reconstruction. METHODS: Diffusion-weighted spin echo imaging with EPI and spiral readouts is performed on a whole-body system equipped with strong gradients (up to 250 mT/m). An expanded encoding model including static off-resonance, coil sensitivities, and magnetic field dynamics is employed for image reconstruction. The acquisitions are performed on a phantom and in vivo (one healthy volunteer and one patient with prostate cancer). The resulting images are compared to conventional dMRI EPI with navigator-based image reconstruction and assessed in terms of their congruence, SNR, tissue contrast, and quantitative parameters. RESULTS: Using the expanded encoding model, high-quality images of the prostate gland are obtained across all b-values (up to 3 ms/µm2), clearly outperforming the results obtained with conventional image reconstruction. Compared to EPI, spiral imaging provides an SNR gain up to 45% within the gland and even higher in the lesion. In addition, prostate dMRI with single-shot spirals at submillimeter in-plane resolution (0.85 mm) is accomplished. CONCLUSION: The combination of strong gradients and an expanded encoding model enables imaging of the prostate with unprecedented image quality. Replacing the commonly used EPI with spirals provides the inherent benefit of shorter echo times and superior readout efficiency and results in higher SNR, which is in particular relevant for considered applications.

Self-calibrated subspace reconstruction for multidimensional MR fingerprinting for simultaneous relaxation and diffusion quantification.

PURPOSE: To propose a new reconstruction method for multidimensional MR fingerprinting (mdMRF) to address shading artifacts caused by physiological motion-induced measurement errors without navigating or gating. METHODS: The proposed method comprises two procedures: self-calibration and subspace reconstruction. The first procedure (self-calibration) applies temporally local matrix completion to reconstruct low-resolution images from a subset of under-sampled data extracted from the k-space center. The second procedure (subspace reconstruction) utilizes temporally global subspace reconstruction with pre-estimated temporal subspace from low-resolution images to reconstruct aliasing-free, high-resolution, and time-resolved images. After reconstruction, a customized outlier detection algorithm was employed to automatically detect and remove images corrupted by measurement errors. Feasibility, robustness, and scan efficiency were evaluated through in vivo human brain imaging experiments. RESULTS: The proposed method successfully reconstructed aliasing-free, high-resolution, and time-resolved images, where the measurement errors were accurately represented. The corrupted images were automatically and robustly detected and removed. Artifact-free T1, T2, and ADC maps were generated simultaneously. The proposed reconstruction method demonstrated robustness across different scanners, parameter settings, and subjects. A high scan efficiency of less than 20 s per slice has been achieved. CONCLUSION: The proposed reconstruction method can effectively alleviate shading artifacts caused by physiological motion-induced measurement errors. It enables simultaneous and artifact-free quantification of T1, T2, and ADC using mdMRF scans without prospective gating, with robustness and high scan efficiency.

Pore size estimation in axon-mimicking microfibers with diffusion-relaxation MRI.

PURPOSE: This study aims to evaluate two distinct approaches for fiber radius estimation using diffusion-relaxation MRI data acquired in biomimetic microfiber phantoms that mimic hollow axons. The methods considered are the spherical mean power-law approach and a T2-based pore size estimation technique. THEORY AND METHODS: A general diffusion-relaxation theoretical model for the spherical mean signal from water molecules within a distribution of cylinders with varying radii was introduced, encompassing the evaluated models as particular cases. Additionally, a new numerical approach was presented for estimating effective radii (i.e., MRI-visible mean radii) from the ground truth radii distributions, not reliant on previous theoretical approximations and adaptable to various acquisition sequences. The ground truth radii were obtained from scanning electron microscope images. RESULTS: Both methods show a linear relationship between effective radii estimated from MRI data and ground-truth radii distributions, although some discrepancies were observed. The spherical mean power-law method overestimated fiber radii. Conversely, the T2-based method exhibited higher sensitivity to smaller fiber radii, but faced limitations in accurately estimating the radius in one particular phantom, possibly because of material-specific relaxation changes. CONCLUSION: The study demonstrates the feasibility of both techniques to predict pore sizes of hollow microfibers. The T2-based technique, unlike the spherical mean power-law method, does not demand ultra-high diffusion gradients, but requires calibration with known radius distributions. This research contributes to the ongoing development and evaluation of neuroimaging techniques for fiber radius estimation, highlights the advantages and limitations of both methods, and provides datasets for reproducible research.

In vivo diffusion MRI of the human heart using a 300 mT/m gradient system.

PURPOSE: This work reports for the first time on the implementation and application of cardiac diffusion-weighted MRI on a Connectom MR scanner with a maximum gradient strength of 300 mT/m. It evaluates the benefits of the increased gradient performance for the investigation of the myocardial microstructure. METHODS: Cardiac diffusion-weighted imaging (DWI) experiments were performed on 10 healthy volunteers using a spin-echo sequence with up to second- and third-order motion compensation ( M 2 $$ {M}_2 $$ and M 3 $$ {M}_3 $$ ) and b = 100 , 450 $$ b=100,450 $$ , and 1000 s / m m 2 $$ \mathrm{s}/\mathrm{m}{\mathrm{m}}^2 $$ (twice the b max $$ {b}_{\mathrm{max}} $$ commonly used on clinical scanners). Mean diffusivity (MD), fractional anisotropy (FA), helix angle (HA), and secondary eigenvector angle (E2A) were calculated for b = [100, 450] s / m m 2 $$ \mathrm{s}/\mathrm{m}{\mathrm{m}}^2 $$ and b = [100, 1000] s / m m 2 $$ \mathrm{s}/\mathrm{m}{\mathrm{m}}^2 $$ for both M 2 $$ {M}_2 $$ and M 3 $$ {M}_3 $$ . RESULTS: The MD values with M 3 $$ {M}_3 $$ are slightly higher than with M 2 $$ {M}_2 $$ with Δ MD = 0 . 05 ± 0 . 05 [ × 1 0 - 3 mm 2 / s ] ( p = 4 e - 5 ) $$ \Delta \mathrm{MD}=0.05\pm 0.05\kern0.3em \left[\times 1{0}^{-3}\kern0.3em {\mathrm{mm}}^2/\mathrm{s}\right]\kern0.3em \left(p=4e-5\right) $$ for b max = 450 s / mm 2 $$ {b}_{\mathrm{max}}=450\kern0.3em \mathrm{s}/{\mathrm{mm}}^2 $$ and Δ MD = 0 . 03 ± 0 . 03 [ × 1 0 - 3 mm 2 / s ] ( p = 4 e - 4 ) $$ \Delta \mathrm{MD}=0.03\pm 0.03\kern0.3em \left[\times \kern0.3em 1{0}^{-3}\kern0.3em {\mathrm{mm}}^2/\mathrm{s}\right]\kern0.3em \left(p=4e-4\right) $$ for b max = 1000 s / mm 2 $$ {b}_{\mathrm{max}}=1000\kern0.3em \mathrm{s}/{\mathrm{mm}}^2 $$ . A reduction in MD is observed by increasing the b max $$ {b}_{\mathrm{max}} $$ from 450 to 1000 s / mm 2 $$ \mathrm{s}/{\mathrm{mm}}^2 $$ ( Δ MD = 0 . 06 ± 0 . 04 [ × 1 0 - 3 mm 2 / s ] ( p = 1 . 6 e - 9 ) $$ \Delta \mathrm{MD}=0.06\pm 0.04\kern0.3em \left[\times \kern0.3em 1{0}^{-3}\kern0.3em {\mathrm{mm}}^2/\mathrm{s}\right]\kern0.3em \left(p=1.6e-9\right) $$ for M 2 $$ {M}_2 $$ and Δ MD = 0 . 08 ± 0 . 05 [ × 1 0 - 3 mm 2 / s ] ( p = 1 e - 9 ) $$ \Delta \mathrm{MD}=0.08\pm 0.05\kern0.3em \left[\times \kern0.3em 1{0}^{-3}\kern0.3em {\mathrm{mm}}^2/\mathrm{s}\right]\kern0.3em \left(p=1e-9\right) $$ for M 3 $$ {M}_3 $$ ). The difference between FA, E2A, and HA was not significant in different schemes ( p > 0 . 05 $$ p>0.05 $$ ). CONCLUSION: This work demonstrates cardiac DWI in vivo with higher b-value and higher order of motion compensated diffusion gradient waveforms than is commonly used. Increasing the motion compensation order from M 2 $$ {M}_2 $$ to M 3 $$ {M}_3 $$ and the maximum b-value from 450 to 1000 s / mm 2 $$ \mathrm{s}/{\mathrm{mm}}^2 $$ affected the MD values but FA and the angular metrics (HA and E2A) remained unchanged. Our work paves the way for cardiac DWI on the next-generation MR scanners with high-performance gradient systems.

Diffusion MRI in prostate cancer with ultra-strong whole-body gradients.

Diffusion-weighted MRI (dMRI) is universally recommended for the detection and classification of prostate cancer (PCa), with PI-RADS recommendations to acquire b-values of ≥1.4 ms/µm2. However, clinical dMRI suffers from a low signal-to-noise ratio (SNR) as the consequence of prolonged echo times (TEs) attributable to the limited gradient power in the range of 40-80 mT/m. To overcome this, MRI systems with strong gradients have been designed but so far have mainly been applied in the brain. The aim of this work was to assess the feasibility, data quality, SNR and contrast-to-noise ratio (CNR) of measurements in PCa with a 300 mT/m whole-body system. A cohort of men without and with diagnosed PCa were imaged on a research-only 3T Connectom Siemens MRI system equipped with a gradient amplitude of 300 mT/m. dMRI at high b-values were acquired using high gradient amplitudes and compared with gradient capabilities mimicking clinical systems. Data artefacts typically amplified with stronger gradients were assessed and their correction evaluated. The SNR gains and lesion-to-healthy tissue CNR were statistically tested investigating the effect of protocol and b-value. The diagnostic quality of the images for different dMRI protocols was assessed by an experienced radiologist using a 5-point Likert scale and an adapted PI-QUAL scoring system. The strong gradients for prostate dMRI allowed a significant gain in SNR per unit time compared with clinical gradients. Furthermore, a 1.6-2.1-fold increase in CNR was observed. Despite the more pronounced artefacts typically associated with strong gradients, a satisfactory correction could be achieved. Smoother and less biased parameter maps were obtained with protocols at shorter TEs. The results of this study show that dMRI in PCa with a whole-body 300-mT/m scanner is feasible without a report of physiological effects, SNR and CNR can be improved compared with lower gradient strengths, and artefacts do not negate the benefits of strong gradients and can be ameliorated. This assessment provides the first essential step towards unveiling the full potential of cutting-edge scanners, now increasingly becoming available, to advance early detection and diagnostic precision.

In vivo evidence of microstructural hypo-connectivity of brain white matter in 22q11.2 deletion syndrome.

22q11.2 deletion syndrome, or 22q11.2DS, is a genetic syndrome associated with high rates of schizophrenia and autism spectrum disorders, in addition to widespread structural and functional abnormalities throughout the brain. Experimental animal models have identified neuronal connectivity deficits, e.g., decreased axonal length and complexity of axonal branching, as a primary mechanism underlying atypical brain development in 22q11.2DS. However, it is still unclear whether deficits in axonal morphology can also be observed in people with 22q11.2DS. Here, we provide an unparalleled in vivo characterization of white matter microstructure in participants with 22q11.2DS (12-15 years) and those undergoing typical development (8-18 years) using a customized magnetic resonance imaging scanner which is sensitive to axonal morphology. A rich array of diffusion MRI metrics are extracted to present microstructural profiles of typical and atypical white matter development, and provide new evidence of connectivity differences in individuals with 22q11.2DS. A recent, large-scale consortium study of 22q11.2DS identified higher diffusion anisotropy and reduced overall diffusion mobility of water as hallmark microstructural alterations of white matter in individuals across a wide age range (6-52 years). We observed similar findings across the white matter tracts included in this study, in addition to identifying deficits in axonal morphology. This, in combination with reduced tract volume measurements, supports the hypothesis that abnormal microstructural connectivity in 22q11.2DS may be mediated by densely packed axons with disproportionately small diameters. Our findings provide insight into the in vivo white matter phenotype of 22q11.2DS, and promote the continued investigation of shared features in neurodevelopmental and psychiatric disorders.

The impact of cumulative obstetric complications and childhood trauma on brain volume in young people with psychotic experiences.

Psychotic experiences (PEs) occur in 5-10% of the general population and are associated with exposure to childhood trauma and obstetric complications. However, the neurobiological mechanisms underlying these associations are unclear. Using the Avon Longitudinal Study of Parents and Children (ALSPAC), we studied 138 young people aged 20 with PEs (n = 49 suspected, n = 53 definite, n = 36 psychotic disorder) and 275 controls. Voxel-based morphometry assessed whether MRI measures of grey matter volume were associated with (i) PEs, (ii) cumulative childhood psychological trauma (weighted summary score of 6 trauma types), (iii) cumulative pre/peri-natal risk factors for psychosis (weighted summary score of 16 risk factors), and (iv) the interaction between PEs and cumulative trauma or pre/peri-natal risk. PEs were associated with smaller left posterior cingulate (pFWE < 0.001, Z = 4.19) and thalamus volumes (pFWE = 0.006, Z = 3.91). Cumulative pre/perinatal risk was associated with smaller left subgenual cingulate volume (pFWE < 0.001, Z = 4.54). A significant interaction between PEs and cumulative pre/perinatal risk found larger striatum (pFWE = 0.04, Z = 3.89) and smaller right insula volume extending into the supramarginal gyrus and superior temporal gyrus (pFWE = 0.002, Z = 4.79), specifically in those with definite PEs and psychotic disorder. Cumulative childhood trauma was associated with larger left dorsal striatum (pFWE = 0.002, Z = 3.65), right prefrontal cortex (pFWE < 0.001, Z = 4.63) and smaller left insula volume in all participants (pFWE = 0.03, Z = 3.60), and there was no interaction with PEs group. In summary, pre/peri-natal risk factors and childhood psychological trauma impact similar brain pathways, namely smaller insula and larger striatum volumes. The effect of pre/perinatal risk was greatest in those with more severe PEs, whereas effects of trauma were seen in all participants. In conclusion, environmental risk factors affect brain networks implicated in schizophrenia, which may increase an individual's propensity to develop later psychotic disorders.

Novel insights into axon diameter and myelin content in late childhood and adolescence.

White matter microstructural development in late childhood and adolescence is driven predominantly by increasing axon density and myelin thickness. Ex vivo studies suggest that the increase in axon diameter drives developmental increases in axon density observed with pubertal onset. In this cross-sectional study, 50 typically developing participants aged 8-18 years were scanned using an ultra-strong gradient magnetic resonance imaging scanner. Microstructural properties, including apparent axon diameter $({d}_a)$, myelin content, and g-ratio, were estimated in regions of the corpus callosum. We observed age-related differences in ${d}_a$, myelin content, and g-ratio. In early puberty, males had larger ${d}_a$ in the splenium and lower myelin content in the genu and body of the corpus callosum, compared with females. Overall, this work provides novel insights into developmental, pubertal, and cognitive correlates of individual differences in apparent axon diameter and myelin content in the developing human brain.

Neuromodulators in Men.

BACKGROUND AND OBJECTIVE: Botulinum toxin treatment is gaining popularity among men for cosmetic purposes driven by workplace competition and a desire for confidence and youthfulness. Because of the unique features of male facial anatomy, careful consideration is necessary during assessment and treatment execution. METHODS: The peer-reviewed literature on male facial anatomy in relation to neuromodulator treatment was analyzed with a particular emphasis on studies involving male subjects and the use of botulinum toxin type A. RESULTS: Anatomic differences in muscle mass and contraction patterns between men and women help guide treatment. Men appear to require higher doses for effective treatment of facial wrinkles and, in the case of glabellar lines, often require double the standard dose for women. Treatment of the frontalis muscle in men, responsible for forehead creases, requires precise dosage and placement to avoid brow ptosis. The lateral canthal wrinkles are often the first area that men seek consultation for. Although FDA approval for lower face regions is lacking, off-label use can still be considered. CONCLUSION: Successful botulinum toxin treatment in men necessitates understanding facial anatomy, customized treatment plans, and appropriate dosing. Further research is warranted to refine protocols and enhance outcomes for male patients.

Neutrophilic dermatosis in a patient with an IKZF1 variant and a review of monogenic autoinflammatory disorders presenting with neutrophilic dermatoses.

Monogenic diseases of immune dysregulation should be considered in the evaluation of children presenting with recurrent neutrophilic dermatoses in association with systemic signs of inflammation, autoimmune disease, hematologic abnormalities, and opportunistic or recurrent infections. We report the case of a 2-year-old boy presenting with a neutrophilic dermatosis, found to have a novel likely pathogenic germline variant of the IKAROS Family Zinc Finger 1 (IKZF1) gene; the mutation likely results in a loss of function dimerization defective protein based on reports and studies of similar variants. IKZF1 variants could potentially lead to aberrant neutrophil chemotaxis and development of neutrophilic dermatoses. Long-term surveillance is required to monitor the development of hematologic malignancy, autoimmunity, immunodeficiency, and infection in patients with pathogenic IKZF1 germline variants.

Update on Blindness From Filler: Review of Prognostic Factors, Management Approaches, and a Century of Published Cases.

Vision loss secondary to aesthetic filler treatment is a rare but disastrous complication. The aim of this review was to update the published cases of blindness after filler injection that have occurred since our group published reviews of 98 cases in 2015 and an additional 48 cases in 2019. A literature review was performed to identify all cases of visual complications caused by filler injection published between September 2018 and March 2023. The cases were analyzed independently and in combination with previously reviewed cases. Analyses were based on the number of cases with data available. A total of 365 new cases of partial or complete vision loss after filler injection were identified. The sites that were highest risk were the nose (40.6%), forehead (27.7%), and glabella (19.0%). The filler injected was hyaluronic acid in 79.6% of cases. The most common associated signs were ptosis (56.2%), ophthalmoplegia (44.1%), pain (31.2%), and skin changes (73.2%). Strokelike features were seen in 19.2% of cases. Of the cases reporting visual outcomes (318), 6.0% experienced complete vision recovery, 25.8% had partial improvement in visual acuity, and 68.2% had no vision recovery. Partially preserved visual acuity at onset was a significant predictor of visual improvement (P < .001). The 3 most common treatments were subcutaneous hyaluronidase at or near the filler site (70.1%), systemic steroids (57.3%), and intraarterial thrombolytic therapy (56.0%). No treatments were significantly associated with visual improvement (P > .05). Although blindness and stroke from fillers is a rare complication, practitioners who inject filler should have a thorough knowledge of prevention and management strategies.

A Multicenter, Randomized, Evaluator-Blinded Study to Examine the Safety and Effectiveness of Hyaluronic Acid Filler in the Correction of Infraorbital Hollows.

BACKGROUND: Hyaluronic acid injections are increasingly administered for correction of infraorbital hollows (IOHs). OBJECTIVES: The objective of this study was to examine the effectiveness (IOH correction) and safety of Restylane Eyelight hyaluronic acid (HAEYE) injections. METHODS: Patients with moderate/severe IOHs, assessed with the Galderma infraorbital hollows scale (GIHS), were randomized to HAEYE injections (by needle/cannula) (Day 1 + optional Month 1 touch-up) or no-treatment control. The primary endpoint was blinded evaluator-reported Month 3 response, defined as ≥1-point GIHS improvement from baseline (both sides, concurrently). Other endpoints examined investigator-reported aesthetic improvement on the Global Aesthetic Improvement Scale (GAIS), patient-reported satisfaction (FACE-Q satisfaction with outcome; satisfaction questionnaire), and adverse events. RESULTS: Overall, 333 patients were randomized. Month 3 GIHS responder rate was significantly higher for HA-EYE (87.4%) vs control (17.7%; P < .001), and comparable between HA-EYE-needle and HA-EYE-cannula groups (P = .967). HAEYE GAIS responder rate was 87.5-97.7% (Months 3-12). Mean FACE-Q Rasch-transformed scores were 64.3-73.5 (HAEYE) vs 14.1-16.2 (control) through Month 12. Patients reported looking younger (≥71%) and less tired (≥79%) with reduced undereye shadows (≥76%) and recovered within 3-5 hours posttreatment. Efficacy was maintained through Month 12 (63.5% GIHS responders) and through Month 18, after Month 12 retreatment (80.3% GIHS responders; 99.4% GAIS responders; FACE-Q scores 72.5-72.8). Forty patients (12.7%) reported typically mild adverse events (4.9% HAEYE-needle; 20.9% HAEYE-cannula). CONCLUSIONS: HAEYE treatment was effective in correcting moderate/severe IOHs at the primary endpoint (Month 3). Efficacy was sustained through Month 12 after first treatment for 63.5% and through Month 18 for 80.3% (after 1 retreatment) with needle or cannula administration. Safety outcomes were reassuring.

Why do students choose to do an extended GP placement?

The drivers for medical students' decision making when considering which Student Selected Component (SSC) to undertake is poorly understood. Furthermore, it is unclear why students undertake a specific SSC allowing them to have an extended placement in GP in their final year. It is known that high quality GP placements encourage students to subsequently choose GP as their career, therefore if the decision-making process of students in this area can be better understood, then this may help inform medical school actions to encourage a greater uptake of these extended placements.Semi-structured interviews were conducted with final year medical students at a Scottish University. Students were selected to provide a mixture of those who had and had not chosen to undertake the extended placement. The data was transcribed and analysed using thematic analysis to generate themes which represented the data.This showed that career intention was a major factor driving SSC choice. Additionally, students sought peer feedback and tended to avoid specific SSCs if they felt a lack of internal motivation. Considering the choice for the extended placement, students tended, again, to choose based on career intentions, and they also based their decision on previous experiences of GP.Career intention and prior experience are key factors in student choice of SSC and whether to undertake an extended GP. In order to address the national shortage of GPs medical schools need to consider how they might influence these drivers.

Temporal Diffusion Ratio (TDR) for imaging restricted diffusion: Optimisation and pre-clinical demonstration.

Temporal Diffusion Ratio (TDR) is a recently proposed dMRI technique (Dell'Acqua et al., proc. ISMRM 2019) which provides contrast between areas with restricted diffusion and areas either without restricted diffusion or with length scales too small for characterisation. Hence, it has a potential for informing on pore sizes, in particular the presence of large axon diameters or other cellular structures. TDR employs the signal from two dMRI acquisitions obtained with the same, large, b-value but with different diffusion gradient waveforms. TDR is advantageous as it employs standard acquisition sequences, does not make any assumptions on the underlying tissue structure and does not require any model fitting, avoiding issues related to model degeneracy. This work for the first time introduces and optimises the TDR method in simulation for a range of different tissues and scanner constraints and validates it in a pre-clinical demonstration. We consider both substrates containing cylinders and spherical structures, representing cell soma in tissue. Our results show that contrasting an acquisition with short gradient duration, short diffusion time and high gradient strength with an acquisition with long gradient duration, long diffusion time and low gradient strength, maximises the TDR contrast for a wide range of pore configurations. Additionally, in the presence of Rician noise, computing TDR from a subset (50% or fewer) of the acquired diffusion gradients rather than the entire shell as proposed originally further improves the contrast. In the last part of the work the results are demonstrated experimentally on rat spinal cord. In line with simulations, the experimental data shows that optimised TDR improves the contrast compared to non-optimised TDR. Furthermore, we find a strong correlation between TDR and histology measurements of axon diameter. In conclusion, we find that TDR has great potential and is a very promising alternative (or potentially complement) to model-based approaches for informing on pore sizes and restricted diffusion in general.

Stimulated Raman histology, a novel method to allow for rapid pathologic examination of unprocessed, fresh prostate biopsies.

INTRODUCTION: Delay between targeted prostate biopsy (PB) and pathologic diagnosis can lead to a concern of inadequate sampling and repeated biopsy. Stimulated Raman histology (SRH) is a novel microscopic technique allowing real-time, label-free, high-resolution microscopic images of unprocessed, unsectioned tissue. This technology holds potential to decrease the time for PB diagnosis from days to minutes. We evaluated the concordance of pathologist interpretation of PB SRH as compared with traditional hematoxylin and eosin (H&E) stained slides. METHODS: Men undergoing prostatectomy were included in an IRB-approved prospective study. Ex vivo 18-gauge PB cores, taken from prostatectomy specimen, were scanned in an SRH microscope (NIO; Invenio Imaging) at 20 microns depth using two Raman shifts: 2845 and 2930 cm-1 , to create SRH images. The cores were then processed as per normal pathologic protocols. Sixteen PB containing a mix of benign and malignant histology were used as an SRH training cohort for four genitourinary pathologists, who were then tested on a set of 32 PBs imaged by SRH and processed by traditional H&E. Sensitivity, specificity, accuracy, and concordance for prostate cancer (PCa) detection on SRH relative to H&E were assessed. RESULTS: The mean pathologist accuracy for the identification of any PCa on PB SRH was 95.7%. In identifying any PCa or ISUP grade group 2-5 PCa, a pathologist was independently able to achieve good and very good concordance (κ: 0.769 and 0.845, respectively; p < 0.001). After individual assessment was completed a pathology consensus conference was held for the interpretation of the PB SRH; after the consensus conference the pathologists' concordance in identifying any PCa was also very good (κ: 0.925, p < 0.001; sensitivity 95.6%; specificity 100%). CONCLUSION: SRH produces high-quality microscopic images that allow for accurate identification of PCa in real-time without need for sectioning or tissue processing. The pathologist performance improved through progressive training, showing that ultimately high accuracy can be obtained. Ongoing SRH evaluation in the diagnostic and treatment setting hold promise to reduce time to tissue diagnosis, while interpretation by convolutional neural network may further improve diagnostic characteristics and broaden use.

White matter microstructure in face and body networks predicts facial expression and body posture perception across development.

Facial expression and body posture recognition have protracted developmental trajectories. Interactions between face and body perception, such as the influence of body posture on facial expression perception, also change with development. While the brain regions underpinning face and body processing are well-defined, little is known about how white-matter tracts linking these regions relate to perceptual development. Here, we obtained complementary diffusion magnetic resonance imaging (MRI) measures (fractional anisotropy [FA], spherical mean Sµ ), and a quantitative MRI myelin-proxy measure (R1), within white-matter tracts of face- and body-selective networks in children and adolescents and related these to perceptual development. In tracts linking occipital and fusiform face areas, facial expression perception was predicted by age-related maturation, as measured by Sµ and R1, as well as age-independent individual differences in microstructure, captured by FA and R1. Tract microstructure measures linking posterior superior temporal sulcus body region with anterior temporal lobe (ATL) were related to the influence of body on facial expression perception, supporting ATL as a site of face and body network convergence. Overall, our results highlight age-dependent and age-independent constraints that white-matter microstructure poses on perceptual abilities during development and the importance of complementary microstructural measures in linking brain structure and behaviour.

Clustering Protein Binding Pockets and Identifying Potential Drug Interactions: A Novel Ligand-Based Featurization Method.

Protein-ligand interactions are essential to drug discovery and drug development efforts. Desirable on-target or multitarget interactions are the first step in finding an effective therapeutic, while undesirable off-target interactions are the first step in assessing safety. In this work, we introduce a novel ligand-based featurization and mapping of human protein pockets to identify closely related protein targets and to project novel drugs into a hybrid protein-ligand feature space to identify their likely protein interactions. Using structure-based template matches from PDB, protein pockets are featured by the ligands that bind to their best co-complex template matches. The simplicity and interpretability of this approach provide a granular characterization of the human proteome at the protein-pocket level instead of the traditional protein-level characterization by family, function, or pathway. We demonstrate the power of this featurization method by clustering a subset of the human proteome and evaluating the predicted cluster associations of over 7000 compounds.

Making space to learn about teaching: expanding teaching horizons through postgraduate education.

Clinicians develop as teachers via many activities, from on-the-job training to formal academic programmes. Yet, understanding how clinicians develop the sensibilities of an educator and an appreciation of the complexity of educational environments is challenging. Studies of teacher development have maintained a relatively narrow definition of educational practice. A more expansive view encompasses clinical teachers' roles in relation to elements beyond learners or content, such as the cultures and other structures of healthcare institutions. In our online Postgraduate Certificate in Clinical Education, space and structure are intentionally created for teachers to think and talk about education with colleagues in other disciplinary contexts. We interviewed 17 students about how their approaches to teaching had changed over a year of part-time study, using their teaching philosophies, written at the start of the programme, as points of contrast. We took an abductive approach to data analysis, drawing on the literature and, unavoidably, our own reflexive interpretations of our practice outside of the research context, such as conversations with students and colleagues; our experiences of teaching and our concurrent research and scholarship. Our themes of repertoire building, perspective shifting, embodied practice, and appreciation of context, describe the increasing complexity of individuals' considerations of teaching. We use our analysis as the basis for a discussion of the blurring of boundaries between staff and students on such programmes as both groups are engaged in an ongoing continuum of development as all teachers, continue to be learners of educational practice. These insights can inform the ways in which postgraduate programmes can make space for clinical teachers to share and reflect on practices, perspectives and contexts.

Increased actual sling wear is associated with better early patient-reported and image-based outcomes after shoulder surgery.

BACKGROUND: Prior studies have failed to show differences in functional outcomes for patient-reported sling use after rotator cuff repair. Temperature-sensing devices are used to more accurately measure brace adherence. The purposes of this study were to quantify actual sling adherence and its predictors and to establish whether increased sling adherence is associated with improved functional and image-based outcomes. METHODS: We performed a prospective cohort study of 65 patients undergoing shoulder surgery requiring ≥4 weeks of postoperative sling use. Temperature-sensing devices were implanted in the slings to monitor sling adherence. Patient-reported sling adherence was determined from a questionnaire. Patients were considered 80% adherent if they wore the sling 16 h/d (112 h/week) when 20 h/d was prescribed. The primary outcomes were patient-reported and actual sling adherence, patient-reported outcomes (American Shoulder and Elbow Surgeons score and visual analog scale pain score) within 12 months postoperatively, and image-based failure based on ultrasound or radiography at 6 weeks and 1 year postoperatively. RESULTS: Patient-reported sling adherence was highly sensitive (82.8%), was poorly specific (28.6%), had low accuracy (53.1%), and was weakly correlated with actual sling adherence (r = 0.32, P = .009). On multivariable logistic regression analysis, male patients were 91% less likely than female patients to be adherent with sling use (odds ratio, 0.09; 95% confidence interval [CI], 0.02-0.42; P = .002). Additionally, obese and morbidly obese patients were 88% (95% CI, 0.02-0.84; P = .033) and 98% (95% CI, 0.002-0.27; P = .003), respectively, less likely than non-obese patients to adhere to sling wear postoperatively. After we controlled for surgical procedure, visual analog scale pain scores were significantly better at 6 weeks (ß = -1.47; 95% CI, -2.88 to -0.05; P = .04) and 3 months (ß = -1.68; 95% CI, -3.28 to -0.08; P = .04) if patients adhered to sling wear. A receiver operating characteristic curve showed that 13.6 hours and 15.4 hours of daily sling wear optimized image-based outcomes at 6 weeks (failure rate, 0% vs. 16%; P = .01) and 1 year (failure rate, 3% vs. 28%; P = .008) postoperatively, respectively. CONCLUSION: The results of this study demonstrate that patient-reported sling adherence is unreliable, adherence can be predicted by female sex and lower body mass index, and increased sling adherence is associated with improved early pain scores and image-based outcomes. These data can help inform future studies using postoperative sling protocols as patient-reported sling adherence is not an accurate method to assess sling use.