Quantitative Foot Muscle Magnetic Resonance Imaging Reliably Measures Disease Progression in Children and Adolescents with Charcot-Marie-Tooth Disease Type 1A.

Quantitative muscle fat fraction (FF) responsiveness is lower in younger Charcot-Marie-Tooth disease type 1A (CMT1A) patients with lower baseline calf-level FF. We investigated the practicality, validity, and responsiveness of foot-level FF in this cohort involving 22 CMT1A patients and 14 controls. The mean baseline foot-level FF was 25.9 ± 20.3% in CMT1A patients, and the 365-day FF (n = 15) increased by 2.0 ± 2.4% (p < 0.001 vs controls). Intrinsic foot-level FF demonstrated large responsiveness (12-month standardized response mean (SRM) of 0.86) and correlated with the CMT examination score (ρ = 0.58, P = 0.01). Intrinsic foot-level FF has the potential to be used as a biomarker in future clinical trials involving younger CMT1A patients. ANN NEUROL 2024;96:170-174.

Investigating the effect of oblique image acquisition on the accuracy of QSM and a robust tilt correction method.

PURPOSE: Quantitative susceptibility mapping (QSM) is used increasingly for clinical research where oblique image acquisition is commonplace, but its effects on QSM accuracy are not well understood. THEORY AND METHODS: The QSM processing pipeline involves defining the unit magnetic dipole kernel, which requires knowledge of the direction of the main magnetic field B ^ 0 $$ {\hat{\boldsymbol{B}}}_{\mathbf{0}} $$ with respect to the acquired image volume axes. The direction of B ^ 0 $$ {\hat{\boldsymbol{B}}}_{\mathbf{0}} $$ is dependent on the axis and angle of rotation in oblique acquisition. Using both a numerical brain phantom and in vivo acquisitions in 5 healthy volunteers, we analyzed the effects of oblique acquisition on magnetic susceptibility maps. We compared three tilt-correction schemes at each step in the QSM pipeline: phase unwrapping, background field removal and susceptibility calculation, using the RMS error and QSM-tuned structural similarity index. RESULTS: Rotation of wrapped phase images gave severe artifacts. Background field removal with projection onto dipole fields gave the most accurate susceptibilities when the field map was first rotated into alignment with B ^ 0 $$ {\hat{\boldsymbol{B}}}_{\mathbf{0}} $$ . Laplacian boundary value and variable-kernel sophisticated harmonic artifact reduction for phase data background field removal methods gave accurate results without tilt correction. For susceptibility calculation, thresholded k-space division, iterative Tikhonov regularization, and weighted linear total variation regularization, all performed most accurately when local field maps were rotated into alignment with B ^ 0 $$ {\hat{\boldsymbol{B}}}_{\mathbf{0}} $$ before susceptibility calculation. CONCLUSION: For accurate QSM, oblique acquisition must be taken into account. Rotation of images into alignment with B ^ 0 $$ {\hat{\boldsymbol{B}}}_{\mathbf{0}} $$ should be carried out after phase unwrapping and before background-field removal. We provide open-source tilt-correction code to incorporate easily into existing pipelines: https://github.com/o-snow/QSM_TiltCorrection.git.

Quantitative MRI outcome measures in CMT1A using automated lower limb muscle segmentation.

BACKGROUND: Lower limb muscle magnetic resonance imaging (MRI) obtained fat fraction (FF) can detect disease progression in patients with Charcot-Marie-Tooth disease 1A (CMT1A). However, analysis is time-consuming and requires manual segmentation of lower limb muscles. We aimed to assess the responsiveness, efficiency and accuracy of acquiring FF MRI using an artificial intelligence-enabled automated segmentation technique. METHODS: We recruited 20 CMT1A patients and 7 controls for assessment at baseline and 12 months. The three-point-Dixon fat water separation technique was used to determine thigh-level and calf-level muscle FF at a single slice using regions of interest defined using Musclesense, a trained artificial neural network for lower limb muscle image segmentation. A quality control (QC) check and correction of the automated segmentations was undertaken by a trained observer. RESULTS: The QC check took on average 30 seconds per slice to complete. Using QC checked segmentations, the mean calf-level FF increased significantly in CMT1A patients from baseline over an average follow-up of 12.5 months (1.15%±1.77%, paired t-test p=0.016). Standardised response mean (SRM) in patients was 0.65. Without QC checks, the mean FF change between baseline and follow-up, at 1.15%±1.68% (paired t-test p=0.01), was almost identical to that seen in the corrected data, with a similar overall SRM at 0.69. CONCLUSIONS: Using automated image segmentation for the first time in a longitudinal study in CMT, we have demonstrated that calf FF has similar responsiveness to previously published data, is efficient with minimal time needed for QC checks and is accurate with minimal corrections needed.

Functional MRI but not white matter fibre dissection identifies language dominance.

OBJECTIVES: Lateralisation of some language pathways has been reported in the literature using diffusion tractography, which is more feasible than functional magnetic resonance imaging (fMRI) in challenging patients. Our retrospective study investigates whether a correlation exists between threshold-independent fMRI language lateralisation and structural lateralisation using tractography in healthy controls and brain tumour patients. METHODS: Fifteen healthy subjects and 61 patients underwent language fMRI and diffusion-weighted MRI. A regional fMRI laterality index (LI) was calculated. Tracts dissected were the arcuate fasciculus (long direct and short indirect tracts), uncinate fasciculus, inferior longitudinal fasciculus, inferior fronto-occipital fasciculus and frontal aslant tract. An asymmetry index (AI) for each tract was calculated using tract volume analysed with single tensor (ST) and spherical deconvolution (SD) models, as well as hindrance modulated orientational anisotropy (HMOA) for SD tracts. Linear regression assessed the correlation between LI and AI. RESULTS: In all subjects, there was no significant correlation between LI and AI for any of the dissected tracts. Significant correlations were only found when handedness for controls and tumour volume for patients were included as covariates. In handedness subgroups, the average AI of some tracts showed the same laterality as LI, and some the opposite. Discordant results were observed for ST- and SD-based AIs. CONCLUSIONS: Our results do not support using tractography in the assessment of language lateralisation. The discordant results between ST and SD indicate that either the structural lateralisation of dissected tracts is less robust than functional lateralisation, or tractography is not sensitive methodology. Other diffusion analysis approaches should be developed. CLINICAL RELEVANCE STATEMENT: Although diffusion tractography may be more feasible than fMRI in challenging tumour patients and where sedation or anaesthesia is required, our results do not currently recommend replacing fMRI with tractography using volume or HMOA in the assessment of language lateralisation. KEY POINTS: • No correlation found between fMRI and tractography in language lateralisation. • Discordance between asymmetry indices of different tractography models and metrics. • Tractography not currently recommended in language lateralisation assessment.

Evidence of nerve hypertrophy in patients with inclusion body myositis on lower limb MRI.

INTRODUCTION/AIMS: Inclusion body myositis (IBM) is a myopathic condition but in some patients has been associated with an axonal length-dependent polyneuropathy. In this study, we quantified the cross-sectional area of the sciatic and tibial nerves in patients with IBM comparing with Charcot-Marie-Tooth disease type 1A (CMT1A) and healthy controls using magnetic resonance neurography (MRN). METHODS: MRN of the sciatic and tibial nerves was performed at 3T using MPRAGE and Dixon acquisitions. Nerve cross-sectional area (CSA) was measured at the mid-thigh and upper third calf regions by an observer blinded to the diagnosis. Correlations were performed between these measurements and clinical data. RESULTS: A total of 20 patients with IBM, 20 CMT1A and 29 healthy controls (age- and sex-matched) were studied. Sciatic nerve CSA was significantly enlarged in patients with IBM and CMT1A compared to controls (sciatic nerve mean CSA 62.3 ± 22.9 mm2 (IBM) vs. 35.5 ± 9.9 mm2 (controls), p < 0.001; and 96.9 ± 35.5 mm2 (CMT1A) vs. 35.5 ± 9.9 mm2 (controls); p < 0.001). Tibial nerve CSA was also enlarged in IBM and CMT1 patients compared to controls. DISCUSSION: MRN reveals significant hypertrophy of the sciatic and tibial nerves in patients with IBM and CMT1A compared to controls. Further studies are needed to correlate with neurophysiological measures and assess whether this finding is useful diagnostically.

Tractography dissection variability: What happens when 42 groups dissect 14 white matter bundles on the same dataset?

White matter bundle segmentation using diffusion MRI fiber tractography has become the method of choice to identify white matter fiber pathways in vivo in human brains. However, like other analyses of complex data, there is considerable variability in segmentation protocols and techniques. This can result in different reconstructions of the same intended white matter pathways, which directly affects tractography results, quantification, and interpretation. In this study, we aim to evaluate and quantify the variability that arises from different protocols for bundle segmentation. Through an open call to users of fiber tractography, including anatomists, clinicians, and algorithm developers, 42 independent teams were given processed sets of human whole-brain streamlines and asked to segment 14 white matter fascicles on six subjects. In total, we received 57 different bundle segmentation protocols, which enabled detailed volume-based and streamline-based analyses of agreement and disagreement among protocols for each fiber pathway. Results show that even when given the exact same sets of underlying streamlines, the variability across protocols for bundle segmentation is greater than all other sources of variability in the virtual dissection process, including variability within protocols and variability across subjects. In order to foster the use of tractography bundle dissection in routine clinical settings, and as a fundamental analytical tool, future endeavors must aim to resolve and reduce this heterogeneity. Although external validation is needed to verify the anatomical accuracy of bundle dissections, reducing heterogeneity is a step towards reproducible research and may be achieved through the use of standard nomenclature and definitions of white matter bundles and well-chosen constraints and decisions in the dissection process.

Prevalence of acute dizziness and vertigo in cortical stroke.

BACKGROUND AND PURPOSE: In posterior circulation stroke, vertigo can be a presenting feature. However, whether isolated hemispheric strokes present with vertigo is less clear, despite a few single case reports in the literature. Here, (a) the prevalence of vertigo/dizziness in acute stroke is explored and (b) the cortical distribution of the lesions in relation to both the known vestibular cortex and the evolution of the symptoms, are considered. METHODS: Structured interviews were conducted in 173 consecutive unselected patients admitted to the hyperacute stroke unit at the University College London Hospitals. The interview was used to evaluate whether the patient was suffering from dizziness and/or vertigo before the onset of the stroke and at the time of the stroke (acute dizziness/vertigo), and the nature of these symptoms. RESULTS: In all, 53 patients had cortical infarcts, of which 21 patients reported acute dizziness. Out of these 21, five patients reported rotational vertigo. Seventeen of the total 53 patients had lesions in known vestibular cortical areas distributed within the insular and parietal opercular cortices. CONCLUSIONS: The prevalence of vertigo in acute cortical strokes was 9%, with no single locus of lesion overlap. There is growing evidence supporting a lateralized vestibular cortex, with speculation that cortical strokes affecting the right hemisphere are more likely to cause vestibular symptoms than left hemispheric strokes. A trend was observed for this association, with the right hemisphere affected in four of five patients who reported spinning vertigo at the onset of the stroke.

World Health Organization Grade II/III Glioma Molecular Status: Prediction by MRI Morphologic Features and Apparent Diffusion Coefficient.

Background A readily implemented MRI biomarker for glioma genotyping is currently lacking. Purpose To evaluate clinically available MRI parameters for predicting isocitrate dehydrogenase (IDH) status in patients with glioma. Materials and Methods In this retrospective study of patients studied from July 2008 to February 2019, untreated World Health Organization (WHO) grade II/III gliomas were analyzed by three neuroradiologists blinded to tissue results. Apparent diffusion coefficient (ADC) minimum (ADCmin) and mean (ADCmean) regions of interest were defined in tumor and normal appearing white matter (ADCNAWM). A visual rating of anatomic features (T1 weighted, T1 weighted with contrast enhancement, T2 weighted, and fluid-attenuated inversion recovery) was performed. Interobserver comparison (intraclass correlation coefficient and Cohen κ) was followed by nonparametric (Kruskal-Wallis analysis of variance) testing of associations between ADC metrics and glioma genotypes, including Bonferroni correction for multiple testing. Descriptors with sufficient concordance (intraclass correlation coefficient, >0.8; κ > 0.6) underwent univariable analysis. Predictive variables (P < .05) were entered into a multivariable logistic regression and tested in an additional test sample of patients with glioma. Results The study included 290 patients (median age, 40 years; interquartile range, 33-52 years; 169 male patients) with 82 IDH wild-type, 107 IDH mutant/1p19q intact, and 101 IDH mutant/1p19q codeleted gliomas. Two predictive models incorporating ADCmean-to-ADCNAWM ratio, age, and morphologic characteristics, with model A mandating calcification result and model B recording cyst formation, classified tumor type with areas under the receiver operating characteristic curve of 0.94 (95% confidence interval [CI]: 0.91, 0.97) and 0.96 (95% CI: 0.93, 0.98), respectively. In the test sample of 49 gliomas (nine IDH wild type, 21 IDH mutant/1p19q intact, and 19 IDH mutant/1p19q codeleted), the classification accuracy was 40 of 49 gliomas (82%; 95% CI: 71%, 92%) for model A and 42 of 49 gliomas (86%; 95% CI: 76%, 96%) for model B. Conclusion Two algorithms that incorporated apparent diffusion coefficient values, age, and tumor morphologic characteristics predicted isocitrate dehydrogenase status in World Health Organization grade II/III gliomas on the basis of standard clinical MRI sequences alone. © RSNA, 2020 Online supplemental material is available for this article.

The functional neuroanatomy of emotion processing in frontotemporal dementias.

Impaired processing of emotional signals is a core feature of frontotemporal dementia syndromes, but the underlying neural mechanisms have proved challenging to characterize and measure. Progress in this field may depend on detecting functional changes in the working brain, and disentangling components of emotion processing that include sensory decoding, emotion categorization and emotional contagion. We addressed this using functional MRI of naturalistic, dynamic facial emotion processing with concurrent indices of autonomic arousal, in a cohort of patients representing all major frontotemporal dementia syndromes relative to healthy age-matched individuals. Seventeen patients with behavioural variant frontotemporal dementia [four female; mean (standard deviation) age 64.8 (6.8) years], 12 with semantic variant primary progressive aphasia [four female; 66.9 (7.0) years], nine with non-fluent variant primary progressive aphasia [five female; 67.4 (8.1) years] and 22 healthy controls [12 female; 68.6 (6.8) years] passively viewed videos of universal facial expressions during functional MRI acquisition, with simultaneous heart rate and pupillometric recordings; emotion identification accuracy was assessed in a post-scan behavioural task. Relative to healthy controls, patient groups showed significant impairments (analysis of variance models, all P < 0.05) of facial emotion identification (all syndromes) and cardiac (all syndromes) and pupillary (non-fluent variant only) reactivity. Group-level functional neuroanatomical changes were assessed using statistical parametric mapping, thresholded at P < 0.05 after correction for multiple comparisons over the whole brain or within pre-specified regions of interest. In response to viewing facial expressions, all participant groups showed comparable activation of primary visual cortex while patient groups showed differential hypo-activation of fusiform and posterior temporo-occipital junctional cortices. Bi-hemispheric, syndrome-specific activations predicting facial emotion identification performance were identified (behavioural variant, anterior insula and caudate; semantic variant, anterior temporal cortex; non-fluent variant, frontal operculum). The semantic and non-fluent variant groups additionally showed complex profiles of central parasympathetic and sympathetic autonomic involvement that overlapped signatures of emotional visual and categorization processing and extended (in the non-fluent group) to brainstem effector pathways. These findings open a window on the functional cerebral mechanisms underpinning complex socio-emotional phenotypes of frontotemporal dementia, with implications for novel physiological biomarker development.

Improving fMRI in signal drop-out regions at 7 T by using tailored radio-frequency pulses: application to the ventral occipito-temporal cortex.

OBJECTIVE: Signal drop-off occurs in echo-planar imaging in inferior brain areas due to field gradients from susceptibility differences between air and tissue. Tailored-RF pulses based on a hyperbolic secant (HS) have been shown to partially recover signal at 3 T, but have not been tested at higher fields. MATERIALS AND METHODS: The aim of this study was to compare the performance of an optimized tailored-RF gradient-echo echo-planar imaging (TRF GRE-EPI) sequence with standard GRE-EPI at 7 T, in a passive viewing of faces or objects fMRI paradigm in healthy subjects. RESULTS: Increased temporal-SNR (tSNR) was observed in the middle and inferior temporal lobes and orbitofrontal cortex of all subjects scanned, but elsewhere tSNR decreased relative to the standard acquisition. In the TRF GRE-EPI, increased functional signal was observed in the fusiform, lateral occipital cortex, and occipital pole, regions known to be part of the visual pathway involved in face-object perception. CONCLUSION: This work highlights the potential of TRF approaches at 7 T. Paired with a reversed-gradient distortion correction to compensate for in-plane susceptibility gradients, it provides an improved acquisition strategy for future neurocognitive studies at ultra-high field imaging in areas suffering from static magnetic field inhomogeneities.

Neural mechanisms underlying song and speech perception can be differentiated using an illusory percept.

The issue of whether human perception of speech and song recruits integrated or dissociated neural systems is contentious. This issue is difficult to address directly since these stimulus classes differ in their physical attributes. We therefore used a compelling illusion (Deutsch et al. 2011) in which acoustically identical auditory stimuli are perceived as either speech or song. Deutsch's illusion was used in a functional MRI experiment to provide a direct, within-subject investigation of the brain regions involved in the perceptual transformation from speech into song, independent of the physical characteristics of the presented stimuli. An overall differential effect resulting from the perception of song compared with that of speech was revealed in right midposterior superior temporal sulcus/right middle temporal gyrus. A left frontotemporal network, previously implicated in higher-level cognitive analyses of music and speech, was found to co-vary with a behavioural measure of the subjective vividness of the illusion, and this effect was driven by the illusory transformation. These findings provide evidence that illusory song perception is instantiated by a network of brain regions that are predominantly shared with the speech perception network.

Multi-vendor reliability of arterial spin labeling perfusion MRI using a near-identical sequence: implications for multi-center studies.

INTRODUCTION: A main obstacle that impedes standardized clinical and research applications of arterial spin labeling (ASL), is the substantial differences between the commercial implementations of ASL from major MRI vendors. In this study, we compare a single identical 2D gradient-echo EPI pseudo-continuous ASL (PCASL) sequence implemented on 3T scanners from three vendors (General Electric Healthcare, Philips Healthcare and Siemens Healthcare) within the same center and with the same subjects. MATERIAL AND METHODS: Fourteen healthy volunteers (50% male, age 26.4±4.7years) were scanned twice on each scanner in an interleaved manner within 3h. Because of differences in gradient and coil specifications, two separate studies were performed with slightly different sequence parameters, with one scanner used across both studies for comparison. Reproducibility was evaluated by means of quantitative cerebral blood flow (CBF) agreement and inter-session variation, both on a region-of-interest (ROI) and voxel level. In addition, a qualitative similarity comparison of the CBF maps was performed by three experienced neuro-radiologists. RESULTS: There were no CBF differences between vendors in study 1 (p>0.1), but there were CBF differences of 2-19% between vendors in study 2 (p<0.001 in most gray matter ROIs) and 10-22% difference in CBF values obtained with the same vendor between studies (p<0.001 in most gray matter ROIs). The inter-vendor inter-session variation was not significantly larger than the intra-vendor variation in all (p>0.1) but one of the ROIs (p<0.001). CONCLUSION: This study demonstrates the possibility to acquire comparable cerebral CBF maps on scanners of different vendors. Small differences in sequence parameters can have a larger effect on the reproducibility of ASL than hardware or software differences between vendors. These results suggest that researchers should strive to employ identical labeling and readout strategies in multi-center ASL studies.

Designing hyperbolic secant excitation pulses to reduce signal dropout in gradient-echo echo-planar imaging.

PURPOSE: To design hyperbolic secant (HS) excitation pulses to reduce signal dropout in the orbitofrontal and inferior temporal regions in gradient-echo echo-planar imaging (GE-EPI) for functional MRI (fMRI) applications. METHODS: An algorithm based on Bloch simulations optimizes the HS pulse parameters needed to give the desired signal response across the range of susceptibility gradients observed in the human head (approximately ±250 µT·m(-1) ). The impact of the HS pulse on the signal, temporal signal-to-noise ratio, blood oxygen level-dependent (BOLD) sensitivity, and ability to detect resting state BOLD signal changes was assessed in six healthy male volunteers at 3T. RESULTS: The optimized HS pulse (µ = 4.25, ß = 3040 Hz, A0 = 12.3 µT, Δf = 4598 Hz) had a near uniform signal response for through-plane susceptibility gradients in the range ±250 µT·m(-1) . Signal, temporal signal-to-noise ratio, BOLD sensitivity, and the detectability of resting state networks were all partially recovered in the orbitofrontal and inferior temporal regions; however, there were signal losses of up to 50% in regions of homogeneous field (and signal loss from in-plane susceptibility gradients remained). CONCLUSION: The HS pulse reduced signal dropout and could be used to acquire task and resting state fMRI data without loss of spatial coverage or temporal resolution.

Lower limb muscle MRI fat fraction is a responsive outcome measure in CMT X1, 1B and 2A.

OBJECTIVE: With potential therapies for many forms of Charcot-Marie-Tooth disease (CMT), responsive outcome measures are urgently needed for clinical trials. Quantitative lower limb MRI demonstrated progressive calf intramuscular fat accumulation in the commonest form, CMT1A with large responsiveness. In this study, we evaluated the responsiveness and validity in the three other common forms, due to variants in GJB1 (CMTX1), MPZ (CMT1B) and MFN2 (CMT2A). METHODS: 22 CMTX1, 21 CMT1B and 21 CMT2A patients and matched controls were assessed at a 1-year interval. Intramuscular fat fraction (FF) was evaluated using three-point Dixon MRI at thigh and calf level along with clinical measures including CMT examination score, clinical strength assessment, CMT-HI and plasma neurofilament light chain. RESULTS: All patient groups had elevated muscle fat fraction at thigh and calf levels, with highest thigh FF and atrophy in CMT2A. There was moderate correlation between calf muscle FF and clinical measures (CMTESv2 rho = 0.405; p = 0.001, ankle MRC strength rho = -0.481; p < 0.001). Significant annualised progression in calf muscle FF was seen in all patient groups (CMTX1 2.0 ± 2.0%, p < 0.001, CMT1B 1.6 ± 2.1% p = 0.004 and CMT2A 1.6 ± 2.1% p = 0.002). Greatest increase was seen in patients with 10-70% FF at baseline (calf 2.7 ± 2.3%, p < 0.0001 and thigh 1.7 ± 2.1%, p = 0.01). INTERPRETATION: Our results confirm that calf muscle FF is highly responsive over 12 months in three additional common forms of CMT which together with CMT1A account for 90% of genetically confirmed cases. Calf muscle MRI FF should be a valuable outcome measure in upcoming CMT clinical trials.

Glioblastoma and radiotherapy: A multicenter AI study for Survival Predictions from MRI (GRASP study).

BACKGROUND: The aim was to predict survival of glioblastoma at 8 months after radiotherapy (a period allowing for completing a typical course of adjuvant temozolomide), by applying deep learning to the first brain MRI after radiotherapy completion. METHODS: Retrospective and prospective data were collected from 206 consecutive glioblastoma, isocitrate dehydrogenase -wildtype patients diagnosed between March 2014 and February 2022 across 11 UK centers. Models were trained on 158 retrospective patients from 3 centers. Holdout test sets were retrospective (n = 19; internal validation), and prospective (n = 29; external validation from 8 distinct centers). Neural network branches for T2-weighted and contrast-enhanced T1-weighted inputs were concatenated to predict survival. A nonimaging branch (demographics/MGMT/treatment data) was also combined with the imaging model. We investigated the influence of individual MR sequences; nonimaging features; and weighted dense blocks pretrained for abnormality detection. RESULTS: The imaging model outperformed the nonimaging model in all test sets (area under the receiver-operating characteristic curve, AUC P = .038) and performed similarly to a combined imaging/nonimaging model (P > .05). Imaging, nonimaging, and combined models applied to amalgamated test sets gave AUCs of 0.93, 0.79, and 0.91. Initializing the imaging model with pretrained weights from 10 000s of brain MRIs improved performance considerably (amalgamated test sets without pretraining 0.64; P = .003). CONCLUSIONS: A deep learning model using MRI images after radiotherapy reliably and accurately determined survival of glioblastoma. The model serves as a prognostic biomarker identifying patients who will not survive beyond a typical course of adjuvant temozolomide, thereby stratifying patients into those who might require early second-line or clinical trial treatment.

Early MRI Predictors of Relapse in Primary Central Nervous System Lymphoma Treated with MATRix Immunochemotherapy.

Primary Central Nervous System Lymphoma (PCNSL) is a highly malignant brain tumour. We investigated dynamic changes in tumour volume and apparent diffusion coefficient (ADC) measurements for predicting outcome following treatment with MATRix chemotherapy in PCNSL. Patients treated with MATRix (n = 38) underwent T1 contrast-enhanced (T1CE) and diffusion-weighted imaging (DWI) before treatment, after two cycles and after four cycles of chemotherapy. Response was assessed using the International PCNSL Collaborative Group (IPCG) imaging criteria. ADC histogram parameters and T1CE tumour volumes were compared among response groups, using one-way ANOVA testing. Logistic regression was performed to examine those imaging parameters predictive of response. Response after two cycles of chemotherapy differed from response after four cycles; of the six patients with progressive disease (PD) after four cycles of treatment, two (33%) had demonstrated a partial response (PR) or complete response (CR) after two cycles. ADCmean at baseline, T1CE at baseline and T1CE percentage volume change differed between response groups (0.005 < p < 0.038) and were predictive of MATRix treatment response (area under the curve: 0.672-0.854). Baseline ADC and T1CE metrics are potential biomarkers for risk stratification of PCNSL patients early during remission induction therapy with MATRix. Standard interim response assessment (after two cycles) according to IPCG imaging criteria does not reliably predict early disease progression in the context of a conventional treatment approach.

Overcoming challenges of translating deep-learning models for glioblastoma: the ZGBM consortium.

OBJECTIVE: To report imaging protocol and scheduling variance in routine care of glioblastoma patients in order to demonstrate challenges of integrating deep-learning models in glioblastoma care pathways. Additionally, to understand the most common imaging studies and image contrasts to inform the development of potentially robust deep-learning models. METHODS: MR imaging data were analysed from a random sample of five patients from the prospective cohort across five participating sites of the ZGBM consortium. Reported clinical and treatment data alongside DICOM header information were analysed to understand treatment pathway imaging schedules. RESULTS: All sites perform all structural imaging at every stage in the pathway except for the presurgical study, where in some sites only contrast-enhanced T1-weighted imaging is performed. Diffusion MRI is the most common non-structural imaging type, performed at every site. CONCLUSION: The imaging protocol and scheduling varies across the UK, making it challenging to develop machine-learning models that could perform robustly at other centres. Structural imaging is performed most consistently across all centres. ADVANCES IN KNOWLEDGE: Successful translation of deep-learning models will likely be based on structural post-treatment imaging unless there is significant effort made to standardise non-structural or peri-operative imaging protocols and schedules.

Optimal MRI methods for direct stereotactic targeting of the subthalamic nucleus and globus pallidus.

OBJECTIVE: Reliable identification of the subthalamic nucleus (STN) and globus pallidus interna (GPi) is critical for deep brain stimulation (DBS) of these structures. The purpose of this study was to compare the visibility of the STN and GPi with various MRI techniques and to assess the suitability of each technique for direct stereotactic targeting. METHODS: MR images were acquired from nine volunteers with T2- and proton density-weighted (PD-W) fast spin echo, susceptibility-weighted imaging (SWI), phase-sensitive inversion recovery and quantitative T1, T2 and T2* mapping sequences. Contrast-to-noise ratios (CNR) for the STN and GPi were calculated for all sequences. Targeting errors on SWI were evaluated on magnetic susceptibility maps. The sequences demonstrating the best conspicuity of DBS target structures (SWI and T2*) were then applied to ten patients with movement disorders, and the CNRs for these techniques were assessed. RESULTS: SWI offers the highest CNR for the STN, but standard PD-W images provide the best CNR for the pallidum. Susceptibility maps indicated that the GPi margins may be shifted slightly on SWI, although no shifts were seen for the STN. CONCLUSION: SWI may improve the visibility of the STN on pre-operative MRI, potentially improving the accuracy of direct stereotactic targeting.

Imaging characteristics of H3 K27M histone-mutant diffuse midline glioma in teenagers and adults.

BACKGROUND: To assess anatomical and quantitative diffusion-weighted MR imaging features in a recently classified lethal neoplasm, H3 K27M histone-mutant diffuse midline glioma [World Health Organization (WHO) IV]. METHODS: Fifteen untreated gliomas in teenagers and adults (median age 19, range, 14-64) with confirmed H3 K27M histone-mutant genotype were analysed at a national referral centre. Morphological characteristics including tumour epicentre(s), T2/FLAIR and Gadolinium enhancement patterns, calcification, haemorrhage and cyst formation were recorded. Multiple apparent diffusion coefficient (ADCmin, ADCmean) regions of interest were sited in solid tumour and normal appearing white matter (ADCNAWM) using post-processing software (Olea Sphere v2.3, Olea Medical). ADC histogram data (2nd, 5th, 10th percentile, median, mean, kurtosis, skewness) were calculated from volumetric tumour segmentations and tested against the regions of interest (ROI) data (Wilcoxon signed rank test). RESULTS: The median interval from imaging to tissue diagnosis was 9 (range, 0-74) days. The structural MR imaging findings varied between individuals and within tumours, often featuring signal heterogeneity on all MR sequences. All gliomas demonstrated contact with the brain midline, and 67% exhibited rim-enhancing necrosis. The mean ROI ADCmin value was 0.84 (±0.15 standard deviation, SD) ×10-3 mm2/s. In the largest tumour cross-section (excluding necrosis), an average ADCmean value of 1.12 (±0.25)×10-3 mm2/s was observed. The mean ADCmin/NAWM ratio was 1.097 (±0.149), and the mean ADCmean/NAWM ratio measured 1.466 (±0.299). With the exception of the 2nd centile, no statistical difference was observed between the regional and histogram derived ADC results. CONCLUSIONS: H3 K27M-mutant gliomas demonstrate variable morphology and diffusivity, commonly featuring moderately low ADC values in solid tumour. Regional ADC measurements appeared representative of volumetric histogram data in this study.