Epithelioid glioblastoma diagnosed 70 years after craniofacial radiotherapy.

The authors report a rare case of most likely radiation-induced glioma (RIG) with epithelioid features and the presence of molecular features consistent with RIG. This occurred 70 years after craniofacial brachytherapy. Such a late development of radiation-induced glioblastoma (RIGBM) and the advanced age of presentation for an epithelioid glioblastoma are both unique in the literature. Despite not receiving the full course of adjuvant chemotherapy after surgery and radiotherapy, the patient displayed no signs of recurrence during a 5-year follow-up. RIGBM should be further studied to reveal potential unique clinical and molecular characteristics, as well as to better predict survival and treatment response.

Improved detection of juxtacortical lesions using highly accelerated double inversion-recovery MRI in patients with multiple sclerosis.

PURPOSE: The purpose of this study was to compare a highly-accelerated double inversion recovery (fast-DIR) sequence using a recent parallel imaging technique (CAIPIRINHA) with a conventional DIR (conv-DIR) sequence for image quality and the detection of juxtacortical and infratentorial multiple sclerosis (MS) lesions. MATERIALS AND METHODS: A total of 38 patients with MS who underwent brain MRI at 3 T between 2020 and 2021 were included. There were 27 women and 12 men with a mean age of 40 ± 12.8 (standard deviation) years (range: 20-59 years). All patients underwent conv-DIR sequence and fast-DIR sequence. Fast-DIR was obtained with a T2-preparation module to improve contrast and an iterative denoising algorithm to compensate noise enhancement. Two blinded readers reported the number of juxtacortical and infratentorial MS lesions for fast-DIR and conv-DIR, confirmed by further consensus reading that was used as the standard of reference. Image quality and contrast were evaluated for fast-DIR and conv-DIR sequences. Comparisons between fast-DIR and conv-DIR sequences were performed using Wilcoxon test and Lin concordance correlation coefficient. RESULTS: Thirty-eight patients were analyzed. Fast-DIR imaging allowed detection of 289 juxtacortical lesions vs. 238 with conv-DIR, corresponding to a significant improved detection rate with fast-DIR (P < 0.001). Conversely, 117 infratentorial lesions were detected with conv-DIR sequence vs. 80 with fast-DIR sequence (P < 0.001). Inter-observer agreement for lesion detection with fast-DIR and conv-DIR was very high (Lin concordance correlation coefficient ranging between 0.86 and 0.96). CONCLUSION: Fast-DIR improves the detection of juxtacortical MS lesions, but is limited for the detection of infratentorial MS lesions.

3-Dimensional Fluid and White Matter Suppression Magnetic Resonance Imaging Sequence Accelerated With Compressed Sensing Improves Multiple Sclerosis Cervical Spinal Cord Lesion Detection Compared With Standard 2-Dimensional Imaging.

OBJECTIVES: Fluid and white matter suppression (FLAWS) is a recently proposed magnetic resonance sequence derived from magnetization-prepared 2 rapid acquisition gradient-echo providing 2 coregistered datasets with white matter- and cerebrospinal fluid-suppressed signal, enabling synthetic imaging with amplified contrast. Although these features are high potential for brain multiple sclerosis (MS) imaging, spinal cord has never been evaluated with this sequence to date. The objective of this work was therefore to assess diagnostic performance and self-confidence provided by compressed-sensing (CS) 3-dimensional (3D) FLAWS for cervical MS lesion detection on a head scan that includes the cervical cord without changing standard procedures. MATERIALS AND METHODS: Prospective 3 T scans (MS first diagnosis or follow-up) acquired between 2019 and 2020 were retrospectively analyzed. All patients underwent 3D CS-FLAWS (duration: 5 minutes 40 seconds), axial T 2 turbo spin echo covering cervical spine from cervicomedullary junction to the same inferior level as FLAWS, and sagittal cervical T 2 /short tau inversion recovery imaging. Two readers performed a 2-stage double-blind reading, followed by consensus reading. Wilcoxon tests were used to compare the number of detected spinal cord lesions and the reader's diagnostic self-confidence when using FLAWS versus the reference 2D T 2 -weighted imaging. RESULTS: Fifty-eight patients were included (mean age, 40 ± 13 years, 46 women, 7 ± 6 years mean disease duration). The CS-FLAWS detected significantly more lesions than the reference T 2 -weighted imaging (197 vs 152 detected lesions, P < 0.001), with a sensitivity of 98% (T 2 -weighted imaging sensitivity: 90%) after consensual reading. Considering the subgroup of patients who underwent sagittal T2 + short tau inversion recovery imaging (Magnetic Resonance Imaging for Multiple Sclerosis subgroup), +250% lesions were detected with FLAWS (63 vs 25 lesions detected, P < 0.001). Mean reading self-confidence was significantly better with CS-FLAWS (median, 5 [interquartile range, 1] [no doubt for diagnosis] vs 4 [interquartile range, 1] [high confidence]; P < 0.001). CONCLUSIONS: Imaging with CS-FLAWS provides an improved cervical spinal cord exploration for MS with increased self-confidence compared with conventional T 2 -weighted imaging, in a clinically acceptable time.

Case Report: Multimodal Functional and Structural Evaluation Combining Pre-operative nTMS Mapping and Neuroimaging With Intraoperative CT-Scan and Brain Shift Correction for Brain Tumor Surgical Resection.

Background: Maximum safe resection of infiltrative brain tumors in eloquent area is the primary objective in surgical neuro-oncology. This goal can be achieved with direct electrical stimulation (DES) to perform a functional mapping of the brain in patients awake intraoperatively. When awake surgery is not possible, we propose a pipeline procedure that combines advanced techniques aiming at performing a dissection that respects the anatomo-functional connectivity of the peritumoral region. This procedure can benefit from intraoperative monitoring with computerized tomography scan (iCT-scan) and brain shift correction. Associated with this intraoperative monitoring, the additional value of preoperative investigation combining brain mapping by navigated transcranial magnetic stimulation (nTMS) with various neuroimaging modalities (tractography and resting state functional MRI) has not yet been reported. Case Report: A 42-year-old left-handed man had increased intracranial pressure (IICP), left hand muscle deficit, and dysarthria, related to an infiltrative tumor of the right frontal lobe with large mass effect and circumscribed contrast enhancement in motor and premotor cortical areas. Spectroscopy profile and intratumoral calcifications on CT-scan suggested an WHO grade III glioma, later confirmed by histology. The aforementioned surgical procedure was considered, since standard awake surgery was not appropriate for this patient. In preoperative time, nTMS mapping of motor function (deltoid, first interosseous, and tibialis anterior muscles) was performed, combined with magnetic resonance imaging (MRI)-based tractography reconstruction of 6 neural tracts (arcuate, corticospinal, inferior fronto-occipital, uncinate and superior and inferior longitudinal fasciculi) and resting-state functional MRI connectivity (rs-fMRI) of sensorimotor and language networks. In intraoperative time, DES mapping was performed with motor evoked response recording and tumor resection was optimized using non-rigid image transformation of the preoperative data (nTMS, tractography, and rs-fMRI) to iCT data. Image guidance was updated with correction for brain shift and tissue deformation using biomechanical modeling taking into account brain elastic properties. This correction was done at crucial surgical steps, i.e., when tumor bulged through the craniotomy after dura mater opening and when approaching the presumed eloquent brain regions. This procedure allowed a total resection of the tumor region with contrast enhancement as well as a complete regression of IICP and dysarthria. Hand paresis remained stable with no additional deficit. Postoperative nTMS mapping confirmed the good functional outcome. Conclusion: This case report and technical note highlights the value of preoperative functional evaluation by nTMS updated intraoperatively with correction of brain deformation by iCT. This multimodal approach may become the optimized technique of reference for patients with brain tumors in eloquent areas that are unsuitable for awake brain surgery.

Post-contrast 3D T1-weighted TSE MR sequences (SPACE, CUBE, VISTA/BRAINVIEW, isoFSE, 3D MVOX): Technical aspects and clinical applications.

Post-contrast three-dimensional T1-weighted imaging of the brain is widely used for a broad range of vascular, inflammatory or tumoral diseases. The variable flip angle 3D TSE sequence is now available from several manufacturers (CUBE, General Electric; SPACE, Siemens; VISTA/BRAINVIEW, Philips; isoFSE, Itachi; 3D MVOX, Canon). Compared to gradient-echo (GRE) techniques, 3D TSE offers the advantages of useful image contrasts and reduction of artifacts from static field inhomogeneity. However, the respective role of 3D TSE and GRE MR sequences remains to be elucidated, particularly in the setting of post-contrast imaging. The purpose of this review was (1) to describe the technical aspects of 3D TSE sequences, (2) to illustrate the main clinical applications of the post-contrast 3D T1-w TSE sequence through clinical cases, (3) to discuss the respective role of post-contrast 3D TSE and GRE imaging in the field of neuroimaging.

Time-of-flight angiography at 7T using TONE double spokes with parallel transmission.

PURPOSE: To demonstrate that fast-kz spokes can be used in parallel transmission to homogenize flip angle ramp profiles (known as TONE) in slab selections, and thereby improve Time-Of-Flight angiography of the whole human brain at 7T. METHODS: B1+ and B0 maps were measured on seven human brains with a z-segmented coil connected to an 8-channel pTx system. Tailored two-spoke pulses were designed under strict hardware and SAR constraints for uniform slab profile before transforming their subpulse waveforms for linearly-increasing flip-angle ramps. Increasing angulations along the feet-head direction were prescribed in 2-slab and 3-slab TOF acquisitions. Excitation patterns were simulated and compared with RF-shimmed (single spoke) ramp pulses. Excitation performances were assessed in ~10-min TOF acquisitions by visually inspecting Maximal Intensity Projections angiograms. RESULTS: The flip-angle ramp fidelity achieved by double spokes inside slabs of interest was improved by 30-40% compared to RF-shimmed ramps. This allowed better homogenizing signal along arteries, and depicting small vessels in distal areas of the brain, in comparison with RF-shimmed ramp pulses or double-spoke uniform excitation. CONCLUSION: Ramp double spokes used in conjunction with parallel transmission yield better blood saturation compensation and more finely resolved TOF angiograms than mere double spokes or ramp single spokes at 7T.

The role of the striatum in linguistic selection: Evidence from Huntington's disease and computational modeling.

Though accumulating evidence indicates that the striatum is recruited during language processing, the specific function of this subcortical structure in language remains to be elucidated. To answer this question, we used Huntington's disease as a model of striatal lesion. We investigated the morphological deficit of 30 early Huntington's disease patients with a novel linguistic task that can be modeled within an explicit theory of linguistic computation. Behavioral results reflected an impairment in HD patients on the linguistic task. Computational model-based analysis compared the behavioral data to simulated data from two distinct lesion models, a selection deficit model and a grammatical deficit model. This analysis revealed that the impairment derives from an increased randomness in the process of selecting between grammatical alternatives, rather than from a disruption of grammatical knowledge per se. Voxel-based morphometry permitted to correlate this impairment to dorsal striatal degeneration. We thus show that the striatum holds a role in the selection of linguistic alternatives, just as in the selection of motor and cognitive programs.

Adenosine Triphosphate Metabolism Measured by Phosphorus Magnetic Resonance Spectroscopy: A Potential Biomarker for Multiple Sclerosis Severity.

BACKGROUND/AIMS: Phosphorus magnetic resonance spectroscopy (31P-MRS) has previously shown abnormal changes in energy metabolites in the brain of multiple sclerosis (MS) patients. However, the relationship between these energy metabolites - particularly adenosine triphosphate (ATP) - and the disease severity remains unclear. The objective of this study was to determine whether measuring ATP metabolites can help to predict disease severity in MS patients. METHODS: 31P-MRS at 3 tesla was performed in 9 relapsing remitting (RRMS), 9 secondary progressive MS patients (SPMS), and 10 age-matched healthy controls. ATP metabolites (expressed as %) in normally appearing white matter of the centrum semiovale were compared between patients and healthy controls. The relationship between Expanded Disability Status Scale (EDSS) and ATP metabolites was evaluated. RESULTS: RRMS and SPMS patients had higher phosphocreatine (PCr) and lower phosphodiesters than healthy controls. In addition, RRMS patients had higher ß-ATP% than SPMS patients. ß-ATP% was negatively correlated with EDSS in all patients. CONCLUSION: Our findings suggest a defective PCr metabolism in both patient groups, and a higher state of energy production in RRMS that might reflect a compensatory mechanism in face of the increased needs. The correlation of ß-ATP with EDSS makes it a candidate biomarker for assessing MS disease severity.

Embodied emotion impairment in Huntington's Disease.

Theories of embodied cognition suggest that perceiving an emotion involves somatovisceral and motoric re-experiencing. Here we suggest taking such an embodied stance when looking at emotion processing deficits in patients with Huntington's Disease (HD), a neurodegenerative motor disorder. The literature on these patients' emotion recognition deficit has recently been enriched by some reports of impaired emotion expression. The goal of the study was to find out if expression deficits might be linked to a more motoric level of impairment. We used electromyography (EMG) to compare voluntary emotion expression from words to emotion imitation from static face images, and spontaneous emotion mimicry in 28 HD patients and 24 matched controls. For the latter two imitation conditions, an underlying emotion understanding is not imperative (even though performance might be helped by it). EMG measures were compared to emotion recognition and to the capacity to identify and describe emotions using alexithymia questionnaires. Alexithymia questionnaires tap into the more somato-visceral or interoceptive aspects of emotion perception. Furthermore, we correlated patients' expression and recognition scores to cerebral grey matter volume using voxel-based morphometry (VBM). EMG results replicated impaired voluntary emotion expression in HD. Critically, voluntary imitation and spontaneous mimicry were equally impaired and correlated with impaired recognition. By contrast, alexithymia scores were normal, suggesting that emotion representations on the level of internal experience might be spared. Recognition correlated with brain volume in the caudate as well as in areas previously associated with shared action representations, namely somatosensory, posterior parietal, posterior superior temporal sulcus (pSTS) and subcentral sulcus. Together, these findings indicate that in these patients emotion deficits might be tied to the "motoric level" of emotion expression. Such a double-sided recognition and expression impairment may have important consequences, interrupting empathy in nonverbal communication both ways (understanding and being understood), independently of intact internal experience of emotion.

Magnetic Resonance Imaging Assessment of Kidney Oxygenation and Perfusion During Sickle Cell Vaso-occlusive Crises.

BACKGROUND: Our understanding of the pathophysiologic processes underlying sickle cell nephropathy remains incomplete. We performed a pilot study to investigate the potential value of magnetic resonance imaging (MRI) for the assessment of kidney oxygenation and detection of potential changes to tissue perfusion and cellular integrity during a vaso-occlusive crisis. STUDY DESIGN: A case-control study. SETTING & PARTICIPANTS: 10 homozygous patients with sickle cell disease (SCD), without kidney disease (based on estimated glomerular filtration rate and albuminuria), underwent renal MRI during a vaso-occlusive crisis episode. The imaging data obtained were compared with those for a second MRI performed at steady state (median, 56 [IQR, 37-72] days after the vaso-occlusive crisis MRI). The control group consisted of 10 apparently healthy individuals. MEASUREMENTS: Deoxyhemoglobin level assessed by R2* value was calculated using the blood oxygen level-dependent technique. The intravoxel incoherent motion diffusion-weighted imaging technique was used to calculate D, D*, and F parameters. RESULTS: Median medullary R2* values on steady-state MRI were significantly higher for patients with SCD than for controls (P=0.01) and did not change significantly during the vaso-occlusive crisis. No significant differences in median cortical R2* values were observed. Both cellular integrity (D) and local perfusion (D* and F) were significantly altered in medullary and cortical areas during vaso-occlusive crises in comparison to steady state in patients with SCD. These parameters did not differ significantly between patients with SCD assessed at steady state and the control group. LIMITATIONS: Small sample size, estimation of glomerular filtration rate according to CKD-EPI creatinine equation without adjustment for race. CONCLUSIONS: Deoxyhemoglobin levels in the medullary area are higher in patients with SCD, during vaso-occlusive crises and at steady state, than in controls. Alterations to the tissue perfusion and cellular integrity of renal parenchyma are a common finding during vaso-occlusive crises that provide additional evidence that a vaso-occlusive crisis may be associated with subclinical kidney injury detectable on MRI.

The Hand Motor Hotspot is not Always Located in the Hand Knob: A Neuronavigated Transcranial Magnetic Stimulation Study.

The hand motor hot spot (hMHS) is one of the most salient parameters in transcranial magnetic stimulation (TMS) practice, notably used for targeting. It is commonly accepted that the hMHS corresponds to the hand representation within the primary motor cortex (M1). Anatomical and imaging studies locate this representation in a region of the central sulcus called the "hand knob". The aim of this study was to determine if the hMHS location corresponds to its expected location at the hand knob. Twelve healthy volunteers and eleven patients with chronic neuropathic pain of various origins, but not related to a brain lesion, were enrolled. Morphological magnetic resonance imaging of the brain was normal in all participants. Both hemispheres were studied in all participants except four (two patients and two healthy subjects). Cortical mapping of the hand motor area was conducted using a TMS-dedicated navigation system and recording motor evoked potentials (MEPs) in the contralateral first dorsal interosseous (FDI) muscle. We then determined the anatomical position of the hMHS, defined as the stimulation site providing the largest FDI-MEPs. In 45 % of hemispheres of normal subjects and 25 % of hemispheres of pain patients, the hMHS was located over the central sulcus, most frequently at the level of the hand knob. However, in the other cases, the hMHS was located outside M1, most frequently anteriorly over the precentral or middle frontal gyrus. This study shows that the hMHS does not always correspond to the hand knob and M1 location in healthy subjects or patients. Therefore, image-guided navigation is needed to improve the anatomical accuracy of TMS targeting, even for M1.

Metabolic Tumour Burden Measured by 18F-FDG PET/CT Predicts Malignant Transformation in Patients with Neurofibromatosis Type-1.

BACKGROUND: To investigate the diagnostic and prognostic performances of 18F-FDG PET/CT measures of metabolic tumour burden in patients with neurofibromatosis type-1 (NF1), suspect of malignant transformation. METHODS: This retrospective study included 49 patients (15-60 years old, 30 women) with a diagnosis of NF1, followed in our Reference Centre for Rare Neuromuscular Diseases, who presented clinical signs of tumour progression (pain, neurological deficit, tumour growth). Quantitative metabolic parameters were measured on 149 tumoral targets, using semi-automatic software and the best cut off values to predict transformation was assessed by Receiver Operating Characteristics (ROC) analysis. Prognostic value of PET/CT metabolic parameters was assessed by Kaplan-Meier estimates of overall survival. RESULTS: Lesions were histologically documented in 40 patients: a sarcomatous transformation was found in 16, a dysplastic neurofibroma (NF) in 7, and a benign NF in 17; in the remaining 9 patients, a minimal follow-up of 12 mo (median 59 mo) confirmed the absence of transformation. The optimal cut off values for detection of malignant transformation were, in decreasing order of area under the ROC curves, a tumour-to-liver (T/L) ratio >2.5, SUVmax > 4.5, total lesion glycolysis (TLG) > 377, total metabolic tumour volume (TMTV) > 88 cm3, and heterogeneity index (HIsuv) > 1.69. The best prognostic marker was the TLG: the 4-y estimates of survival were 97% [95% CI, 90% - 100%] in patients with TLG ≤ 377 vs. 27% [95% CI, 5% - 49%] in patients with TLG > 377 (P < 0.0001; χ2 27.85; hazard ratio 13.27 [95% CI, 3.72-47.35]). T/L ratio, SUVmax and TMTV demonstrated slightly lower performance to predict survival, with χ2 ranging 14.41-19.12. The HIsuv index was not predictive of survival. CONCLUSION: Our study demonstrates that TLG and TMTV, as PET/CT measures of metabolic tumour burden, may be used clinically to identify sarcomatous transformation in patients with NF1 and predict overall survival, with a higher specificity for the TLG. Conventional measures such as the SUVmax, and T/L ratio also demonstrate high prognostic value.

Three-dimensional SPACE fluid-attenuated inversion recovery at 3 T to improve subthalamic nucleus lead placement for deep brain stimulation in Parkinson's disease: from preclinical to clinical studies.

OBJECTIVE Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is a well-established therapy for motor symptoms in patients with pharmacoresistant Parkinson's disease (PD). However, the procedure, which requires multimodal perioperative exploration such as imaging, electrophysiology, or clinical examination during macrostimulation to secure lead positioning, remains challenging because the STN cannot be reliably visualized using the gold standard, T2-weighted imaging (T2WI) at 1.5 T. Thus, there is a need to improve imaging tools to better visualize the STN, optimize DBS lead implantation, and enlarge DBS diffusion. METHODS Gradient-echo sequences such as those used in T2WI suffer from higher distortions at higher magnetic fields than spin-echo sequences. First, a spin-echo 3D SPACE (sampling perfection with application-optimized contrasts using different flip angle evolutions) FLAIR sequence at 3 T was designed, validated histologically in 2 nonhuman primates, and applied to 10 patients with PD; their data were clinically compared in a double-blind manner with those of a control group of 10 other patients with PD in whom STN targeting was performed using T2WI. RESULTS Overlap between the nonhuman primate STNs segmented on 3D-histological and on 3D-SPACE-FLAIR volumes was high for the 3 most anterior quarters (mean [± SD] Dice scores 0.73 ± 0.11, 0.74 ± 0.06, and 0.60 ± 0.09). STN limits determined by the 3D-SPACE-FLAIR sequence were more consistent with electrophysiological edges than those determined by T2WI (0.9 vs 1.4 mm, respectively). The imaging contrast of the STN on the 3D-SPACE-FLAIR sequence was 4 times higher (p < 0.05). Improvement in the Unified Parkinson's Disease Rating Scale Part III score (off medication, on stimulation) 12 months after the operation was higher for patients who underwent 3D-SPACE-FLAIR-guided implantation than for those in whom T2WI was used (62.2% vs 43.6%, respectively; p < 0.05). The total electrical energy delivered decreased by 36.3% with the 3D-SPACE-FLAIR sequence (p < 0.05). CONCLUSIONS 3D-SPACE-FLAIR sequences at 3 T improved STN lead placement under stereotactic conditions, improved the clinical outcome of patients with PD, and increased the benefit/risk ratio of STN-DBS surgery.

A cortical-subcortical syntax pathway linking Broca's area and the striatum.

Combinatorial syntax has been shown to be underpinned by cortical key regions such as Broca's area and temporal cortices, and by subcortical structures such as the striatum. The cortical regions are connected via several cortico-to-cortical tracts impacting syntactic processing (e.g., the arcuate) but it remains unclear whether and how the striatum can be integrated into this cortex-centered syntax network. Here, we used a systematic stepwise approach to investigate the existence and syntactic function of an additional deep Broca-striatum pathway. We first asked 15 healthy controls and 12 patients with frontal/striatal lesions to perform three syntax tests. The results obtained were subjected to voxel-based lesion-symptom mapping (VLSM) to provide an anatomo-functional approximation of the pathway. The significant VLSM clusters were then overlapped with the probability maps of four cortico-cortical language tracts generated for 12 healthy participants (arcuate, extreme capsule fiber system, uncinate, aslant), including a probabilistic Broca-striatum tract. Finally, we carried out quantitative analyses of the relationship between the lesion load along the tracts and syntactic processing, by calculating tract-lesion overlap for each patient and analyzing the correlation with syntactic data. Our findings revealed a Broca-striatum tract linking BA45 with the left caudate head and overlapping with VLSM voxel clusters relating to complex syntax. The lesion load values for this tract were correlated with complex syntax scores, whereas no such correlation was observed for the other tracts. These results extend current syntax-network models, by adding a deep "Broca-caudate pathway," and are consistent with functional accounts of frontostriatal circuits.

Bilateral thalamic stimulation induces insomnia in patients treated for intractable tremor.

STUDY OBJECTIVES: To explore the influence of acute bilateral ventral intermediate thalamic nucleus (VIM) stimulation on sleep. DESIGN: Three consecutive full-night polysomnography recordings were made in the laboratory. After the habituation night, a random order for night ON-stim and OFF-stim was applied for the second and third nights. SETTING: Sleep disorders unit of a university hospital. PATIENTS: Eleven patients with bilateral stimulation of the ventral intermediate nucleus of the thalamus (VIM) for drug-resistant tremor. MEASUREMENTS: Sleep measures on polysomnography. RESULTS: Total sleep time was reduced during night ON-stim compared to OFF- stim, as well as rapid eye movement sleep percentage while the percentage of N2 increased. Wakefulness after sleep onset time was increased. CONCLUSION: Our results show that bilateral stimulation of the VIM nuclei reduces sleep and could be associated with insomnia.