Quantitative susceptibility mapping for susceptibility source separation with adaptive relaxometric constant estimation (QSM-ARCS) from solely gradient-echo data.

To separate the contributions of paramagnetic and diamagnetic sources within a voxel, a magnetic susceptibility source separation method based solely on gradient-echo data has been developed. To measure the opposing susceptibility sources more accurately, we propose a novel single-orientation quantitative susceptibility mapping method with adaptive relaxometric constant estimation (QSM-ARCS) for susceptibility source separation. Moreover, opposing susceptibilities and their anisotropic effects were determined in healthy volunteers in the white matter. Multiple spoiled gradient echo and diffusion tensor imaging of ten healthy volunteers was obtained using a 3 T magnetic resonance scanner. After the opposing susceptibility and fractional anisotropy (FA) maps had been reconstructed, the parametric maps were spatially normalized. To evaluate the agreements of QSM-ARCS against the susceptibility source separation method using R2 and R2* maps (χ-separation) by Bland-Altman plots, the opposing susceptibility values were measured using white and deep gray matter atlases. We then evaluated the relationships between the opposing susceptibilities and FAs in the white matter and used a field-to-fiber angle to assess the fiber orientation dependencies of the opposing susceptibilities. The susceptibility maps in QSM-ARCS were successfully reconstructed without large artifacts. In the Bland-Altman analyses, the opposing QSM-ARCS susceptibility values excellently agreed with the χ-separation maps. Significant inverse and proportional correlations were observed between FA and the negative and positive susceptibilities estimated by QSM-ARCS. The fiber orientation dependencies of the negative susceptibility represented a nonmonotonic feature. Conversely, the positive susceptibility increased linearly with the fiber angle with respect to the B0 field. The QSM-ARCS could accurately estimate the opposing susceptibilities, which were identical values of χ-separation, even using gradient echo alone. The opposing susceptibilities might offer direct biomarkers for assessment of the myelin and iron content in glial cells and, through the underlying magnetic sources, provide biologic insights toward clinical transition.

Artificial intelligence-assisted volume isotropic simultaneous interleaved bright- and black-blood examination for brain metastases.

PURPOSE: To verify the effectiveness of artificial intelligence-assisted volume isotropic simultaneous interleaved bright-/black-blood examination (AI-VISIBLE) for detecting brain metastases. METHODS: This retrospective study was approved by our institutional review board and the requirement for written informed consent was waived. Forty patients were included: 20 patients with and without brain metastases each. Seven independent observers (three radiology residents and four neuroradiologists) participated in two reading sessions: in the first, brain metastases were detected using VISIBLE only; in the second, the results of the first session were comprehensively evaluated by adding AI-VISIBLE information. Sensitivity, diagnostic performance, and false positives/case were evaluated. Diagnostic performance was assessed using a figure-of-merit (FOM). Sensitivity and false positives/case were evaluated using McNemar and paired t-tests, respectively. RESULTS: The McNemar test revealed a significant difference between VISIBLE with/without AI information (P < 0.0001). Significantly higher sensitivity (94.9 ± 1.7% vs. 88.3 ± 5.1%, P = 0.0028) and FOM (0.983 ± 0.009 vs. 0.972 ± 0.013, P = 0.0063) were achieved using VISIBLE with AI information vs. without. No significant difference was observed in false positives/case with and without AI information (0.23 ± 0.19 vs. 0.18 ± 0.15, P = 0.250). AI-assisted results of radiology residents became comparable to results of neuroradiologists (sensitivity, FOM: 85.9 ± 3.4% vs. 90.0 ± 5.9%, 0.969 ± 0.016 vs. 0.974 ± 0.012 without AI information; 94.8 ± 1.3% vs. 95.0 ± 2.1%, 0.977 ± 0.010 vs. 0.988 ± 0.005 with AI information, respectively). CONCLUSION: AI-VISIBLE improved the sensitivity and performance for diagnosing brain metastases.

Salvage radiotherapy for locoregional recurrence of esophageal cancer after surgery.

OBJECTIVE: There is no consensus on the optimal treatment for patients with locoregional recurrence of esophageal cancer after surgery. The objective of this study was to investigate the outcomes and prognostic factors associated with salvage radiotherapy in patients with locoregional recurrence of esophageal cancer after surgery. METHODS: We reviewed 80 patients with locoregional recurrence of esophageal cancer after surgery who were treated with radiotherapy. The median dose was 60 Gy, and 29 patients (36%) received elective nodal irradiation. Fifty-three patients (66%) received concurrent chemotherapy (mostly 5-fluorouracil and cisplatin) during radiotherapy. Overall survival, progression-free survival and in-field recurrence rate were assessed. RESULTS: The median follow-up period was 17 months. Two-year overall survival, progression-free survival and in-field recurrence rate were 50.3%, 23.5% and 41.3%, respectively. On multivariate analysis, a maximum diameter of locoregional recurrence lesions <30 mm was associated with higher overall survival (P = 0.044). Disease-free interval between surgery and locoregional recurrence >14 months was associated with higher PFS (P = 0.003). Late grade 3 toxicities occurred in three patients (3.8%). No grade 4 or higher toxicity was observed. CONCLUSIONS: Salvage radiotherapy demonstrated efficacy in achieving in-field control with acceptable toxicity. However, the high rate of out-of-field metastases led to poor progression-free survival and overall survival, particularly in cases involving large lesions and a short disease-free interval. A prospective study is warranted to establish a treatment strategy, particularly considering the combined use of effective anti-cancer drugs.

[Ectopic Injection of Hydrogel Spacer in IMRT for Prostate Cancer-A Case Study].

A hydrogel spacer injection between the prostate and rectum is reported to reduce the risk of rectal toxicity in radiotherapy for prostate cancer. We present a case of an ectopic injection of hydrogel spacer. The patient was a 77-year-old male with intermediate-risk prostate cancer. It was planned that he would receive intensity modulated radiation therapy(IMRT), and a hydrogel spacer was inserted. Three days after insertion, the patient had a fever of 38.6℃ and presented frequent urination and perineal pain. Swelling and heat sensation were observed in the perineum. CRP was 12.00 mg/dL and the white blood cell count was as high as 9,300/µL. T2-weighted images showed a 5.3×1.9 cm high-intensity area around the lower urethra. Ectopic injection of hydrogel spacer and concomitant infection were diagnosed. Upon administering antibiotic treatment, his symptoms and inflammation improved immediately. Four months after hydrogel spacer insertion, T2-weighted images showed a high-intensity area in the lower urethra and around the ischial bone, which was attributed to the remaining hydrogel spacer. The hydrogel spacer and his symptoms completely disappeared at 9 months after hydrogel spacer insertion.

Acute genitourinary toxicity of pencil beam scanning proton therapy for localized prostate cancer: utility of the transition zone index and average urinary flow rate in predicting acute urinary retention.

BACKGROUND: The purpose of this study was to evaluate the incidence of acute genitourinary toxicities in patients undergoing pencil beam scanning proton therapy for prostate cancer and investigate predictive factors associated with acute urinary retention. METHODS: A total of 227 patients treated between 2018 and 2021 were divided into the normo-fractionated proton therapy group (n = 107) and the moderately hypo-fractionated proton therapy group (n = 120), with prescribed doses of 76-78 Gy relative biological effectiveness in 38-39 fractions and 60-63 Gy relative biological effectiveness in 20-21 fractions, respectively. Uroflowmetry parameters and the transition zone index were prospectively evaluated. RESULTS: Forty-five patients (42%) in the normo-fractionated proton therapy and 33 (28%) in the moderately hypo-fractionated proton therapy developed acute grade 2 genitourinary toxicities (P = 0.02). The most common acute genitourinary toxicity was acute urinary retention. Thirty-nine patients (36%) treated with normo-fractionated proton therapy and 27 (23%) treated with moderately hypo-fractionated proton therapy developed grade 2 acute urinary retention (P = 0.02). No patients developed grade ≥ 3 toxicity. Univariate analysis showed the transition zone index, prostate volume, international prostate symptom score, voided volume, maximum flow rate and average flow rate were associated with grade 2 acute urinary retention. Multivariate analysis in both groups revealed the transition zone index (P = 0.025 and 0.029) and average flow rate (P = 0.039 and 0.044) were predictors of grade 2 acute urinary retention. CONCLUSIONS: The incidence of acute genitourinary toxicities was lower in the moderately hypo-fractionated proton therapy compared with the normo-fractionated proton therapy. Lower pretreatment average flow rate and a higher transition zone index were useful predictors of grade 2 acute urinary retention.

[Case of Long-Term Response to Radiotherapy for Intramedullary Spinal Cord Metastasis from Ovarian Cancer after Surgery].

Intramedullary spinal cord metastasis(ISCM)often causes spinal cord neuropathy and should be treated as an oncologic emergency. However, it recurs in most cases after treatment, ISCM is a disease with a very unfavorable prognosis. Herein, we report a successfully treated case of ISCM with emergent and high-dose radiotherapy. A 53-year-old woman had difficulty walking without assistance 2 years after surgery for ovarian cancer. She received emergent radiotherapy at a total dose of 50 Gy in 25 fractions. Her neurological symptoms dramatically improved over 3 weeks after radiotherapy. ISCM has been controlled using the imaging tests at 5 years after radiotherapy. We believe that both emergent and high-dose radiotherapy were effective for ISCM.

Increased functional connectivity between presupplementary motor area and inferior frontal gyrus associated with the ability of motor response inhibition in obsessive-compulsive disorder.

Recent evidence suggests that presupplementary motor area (pre-SMA) and inferior frontal gyrus (IFG) play an important role in response inhibition. However, no study has investigated the relationship between these brain networks at resting-state and response inhibition in obsessive-compulsive disorder (OCD). We performed resting-state functional magnetic resonance imaging scans and then measured the response inhibition of 41 medication-free OCD patients and 49 healthy control (HC) participants by using the stop-signal task outside the scanner. We explored the differences between OCD and HC groups in the functional connectivity of pre-SMA and IFG associated with the ability of motor response inhibition. OCD patients showed a longer stop-signal reaction time (SSRT). Compared to HC, OCD patients exhibit different associations between the ability of motor response inhibition and the functional connectivity between pre-SMA and IFG, inferior parietal lobule, dorsal anterior cingulate cortex, insula, and anterior prefrontal cortex. Additional analysis to investigate the functional connectivity difference from the seed ROIs to the whole brain voxels revealed that, compared to HC, OCD exhibited greater functional connectivity between pre-SMA and IFG. Also, this functional connectivity was positively correlated with the SSRT score. These results provide additional insight into the characteristics of the resting-state functional connectivity of the regions belonging to the cortico-striato-thalamo-cortical circuit and the cingulo-opercular salience network, underlying the impaired motor response inhibition of OCD. In particular, we emphasize the importance of altered functional connectivity between pre-SMA and IFG for the pathophysiology of motor response inhibition in OCD.

Daily irradiation versus irradiation at two- to three-day intervals in stereotactic radiotherapy for patients with 1-5 brain metastases: study protocol for a multicenter open-label randomized phase II trial.

BACKGROUND: Radiobiological daily changes within tumors are considered to be quite different between stereotactic radiotherapy (SRT) (e.g., 50 Gy in 4 fractions) and conventional radiotherapy (e.g., 60 Gy in 30 fractions). We aim to assess the optimal interval of irradiation in SRT and compare outcomes of daily irradiation with irradiation at two- to three-day intervals in SRT for patients with one to five brain metastases (BM). METHODS: This study is conducted as a multicenter open-label randomized phase II trial. Patients aged 20 or older with one to five BM, less than 3.0 cm diameter, and Karnofsky Performance Status ≥70 are eligible. A total of 70 eligible patients will be enrolled. After stratifying by the number of BMs (1, 2 vs. 3-5) and diameter of the largest tumor (< 2 cm vs. ≥ 2 cm), we randomly assigned patients (1:1) to receive daily irradiation (Arm 1), or irradiation at two- to three-day intervals (Arm 2). Both arms are performed with total dose of 27-30 Gy in 3 fractions. The primary endpoint is an intracranial local control rate, defined as intracranial local control at initially treated sites. We use a randomized phase II screening design with a two-sided α of 0∙20. The phase II trial is positive with p < 0.20. All analyses are intention to treat. This study is registered with the UMIN-clinical trials registry, number UMIN000048728. DISCUSSION: This study will provide an assessment of the impact of SRT interval on local control, survival, and toxicity for patients with 1-5 BM. The trial is ongoing and is recruiting now. TRIAL REGISTRATION: UMIN000048728. Date of registration: August 23, 2022. https://center6.umin.ac.jp/cgi-bin/ctr/ctr_view_reg.cgi?recptno=R000055515 .

A deep convolutional neural network-based automatic detection of brain metastases with and without blood vessel suppression.

OBJECTIVES: To develop an automated model to detect brain metastases using a convolutional neural network (CNN) and volume isotropic simultaneous interleaved bright-blood and black-blood examination (VISIBLE) and to compare its diagnostic performance with the observer test. METHODS: This retrospective study included patients with clinical suspicion of brain metastases imaged with VISIBLE from March 2016 to July 2019 to create a model. Images with and without blood vessel suppression were used for training an existing CNN (DeepMedic). Diagnostic performance was evaluated using sensitivity and false-positive results per case (FPs/case). We compared the diagnostic performance of the CNN model with that of the twelve radiologists. RESULTS: Fifty patients (30 males and 20 females; age range 29-86 years; mean 63.3 ± 12.8 years; a total of 165 metastases) who were clinically diagnosed with brain metastasis on follow-up were used for the training. The sensitivity of our model was 91.7%, which was higher than that of the observer test (mean ± standard deviation; 88.7 ± 3.7%). The number of FPs/case in our model was 1.5, which was greater than that by the observer test (0.17 ± 0.09). CONCLUSIONS: Compared to radiologists, our model created by VISIBLE and CNN to diagnose brain metastases showed higher sensitivity. The number of FPs/case by our model was greater than that by the observer test of radiologists; however, it was less than that in most of the previous studies with deep learning. KEY POINTS: • Our convolutional neural network based on bright-blood and black-blood examination to diagnose brain metastases showed a higher sensitivity than that by the observer test. • The number of false-positives/case by our model was greater than that by the previous observer test; however, it was less than those from most previous studies. • In our model, false-positives were found in the vessels, choroid plexus, and image noise or unknown causes.

Volumetric study reveals the relationship between outcome and early radiographic response during bevacizumab-containing chemoradiotherapy for unresectable glioblastoma.

PURPOSE: Although we have shown the clinical benefit of bevacizumab (BEV) in the treatment of unresectable newly diagnosed glioblastomas (nd-GBM), the relationship between early radiographic response and survival outcome remains unclear. We performed a volumetric study of early radiographic responses in nd-GBM treated with BEV. METHODS: Twenty-two patients with unresectable nd-GBM treated with BEV during concurrent temozolomide radiotherapy were analyzed. An experienced neuroradiologist interpreted early responses on fluid-attenuated inversion recovery (FLAIR) and gadolinium-enhanced T1-weighted images (GdT1WI). Volumetric changes were evaluated using diffusion-weighted imaging (DWI) and GdT1WI according to the Response Assessment in Neuro-Oncology (RANO) criteria. The results were categorized into improved (complete response [CR] or partial response [PR]) or non-improved (stable disease [SD] or progressive disease [PD]) groups; outcomes were compared using Kaplan-Meier analysis. RESULTS: The volumetric GdT1WI improvement was a significant predictive factor for overall survival (OS) prolongation (p = 0.0093, median OS: 24.7 vs. 13.6 months); however, FLAIR and DWI images were not predictive. The threshold for the neuroradiologist's interpretation of improvement in GdT1WI was nearly 20% of volume reduction, which was lesser than 50%, the definition of PR applied in the RANO criteria. However, even less stringent neuroradiologist interpretation could successfully predict OS prolongation (improved vs. non-improved: p = 0.0067, median OS: 17.6 vs. 8.3 months). Significant impact of OS on the early response in volumetric GdT1WI was observed within the cut-off range of 20-50% (20%, p = 0.0315; 30%, p = 0.087; 40%, p = 0.0456). CONCLUSIONS: Early response during BEV-containing chemoradiation can be a predictive indicator of patient outcome in unresectable nd-GBM.

Diagnostic accuracy for the epileptogenic zone detection in focal epilepsy could be higher in FDG-PET/MRI than in FDG-PET/CT.

OBJECTIVES: To examine the utility of FDG-PET/MRI in patients with epilepsy by comparing the diagnostic accuracy of PET/MRI and PET/CT in epileptogenic zone (EZ) detection. METHODS: This prospective study included 31 patients (17 males, 14 females) who underwent surgical resection for EZ. All patients were first scanned using FDG-PET/CT followed immediately with FDG-PET/MRI. Two series of PET plus standalone MR images were interpreted independently by five board-certified radiologists. A 4-point visual score was used to assess image quality. Sensitivities and visual scores from both PETs and standalone MRI were compared using the McNemar test with Bonferroni correction and Dunn's multiple comparisons test. RESULTS: The EZs were confirmed histopathologically via resection as hippocampal sclerosis (n = 11, 35.5%), gliosis (n = 8, 25.8%), focal cortical dysplasia (n = 6, 19.4%), and brain tumours (n = 6, 19.4%) including cavernous haemangioma (n = 3), dysembryoplastic neuroepithelial tumour (n = 1), ganglioglioma (n = 1), and polymorphous low-grade neuroepithelial tumour of the young (n = 1). The sensitivity of FDG-PET/MRI was significantly higher than that of FDG-PET/CT and standalone MRI (FDG-PET/MRI vs. FDG-PET/CT vs. standalone MRI; 77.4-90.3% vs. 58.1-64.5% vs. 45.2-80.6%, p < 0.0001, respectively). The visual scores derived from FDG-PET/MRI were significantly higher than those of FDG-PET/CT, as well as standalone MRI (2.8 ± 1.2 vs. 2.0 ± 1.1 vs. 2.1 ± 1.2, p < 0.0001, respectively). Compared to FDG-PET/CT, FDG-PET/MRI increased the visual score (51.9%, increased visual scores of 2 and 3). CONCLUSIONS: The diagnostic accuracy for the EZ detection in focal epilepsy could be higher in FDG-PET/MRI than in FDG-PET/CT. KEY POINTS: • Sensitivity of FDG-PET/MRI was significantly higher than that of FDG-PET/CT and standalone MRI (FDG-PET/MRI vs. FDG-PET/CT vs. standalone MRI; 77.4-90.3% vs. 58.1-64.5% vs. 45.2-80.6%, p < 0.0001, respectively). • Visual scores derived from FDG-PET/MRI were significantly higher than those of FDG-PET/CT and standalone MRI (2.8 ± 1.2 vs. 2.0 ± 1.1 vs. 2.1 ± 1.2, p < 0.0001, respectively). • Compared to FDG-PET/CT, FDG-PET/MRI increased the visual score (51.9%, increased visual scores of 2 and 3).

First-line bevacizumab contributes to survival improvement in glioblastoma patients complementary to temozolomide.

INTRODUCTION: First-line bevacizumab (BEV) is now available as a treatment option for glioblastoma patients with severe clinical conditions in Japan. However, the survival benefits remain controversial. To elucidate these potential survival benefits, we retrospectively analyzed survival in glioblastoma patients receiving BEV. METHODS: We analyzed survival in 120 patients with IDH-wild type glioblastoma treated from 2002 to 2018. Overall survival (OS) was assessed in three treatment era subgroups [pre-temozolomide (TMZ), TMZ, and TMZ-BEV], and the correlations of prognostic factors with survival were evaluated. RESULTS: An improvement in survival was observed after BEV approval (median OS in the pre-TMZ, TMZ, and TMZ-BEV eras: 14.6, 14.9, and 22.1 months, respectively). A Cox proportional hazards model identified extent of resection and MGMT methylation status as significant prognostic factors in the TMZ era; however, these factors were not significant in the TMZ-BEV era. In subgroup analyses, patients with MGMT methylation had improved OS after TMZ introduction (pre-TMZ vs. TMZ, 18.5 vs. 28.1 months; P = 0.13), and those without MGMT methylation had significantly increased OS after BEV approval (TMZ vs. TMZ-BEV, 12.2 vs. 16.7 months; P = 0.04). CONCLUSIONS: Our findings imply that optional first-line administration of BEV can overcome the impact of conventional risk factors and prolong survival complementary to TMZ. The patient subgroups benefitting from TMZ and BEV did not seem to overlap, and stratification based on risk factors, including MGMT methylation status, might be effective for selecting patients in whom BEV should be preferentially used as a first-line therapy.

Vessel-selective 4D-MR angiography using super-selective pseudo-continuous arterial spin labeling may be a useful tool for assessing brain AVM hemodynamics.

OBJECTIVES: To evaluate the usefulness of 4D-MR angiography based on super-selective pseudo-continuous ASL combined with keyhole and view-sharing (4D-S-PACK) for vessel-selective visualization and to examine the ability of this technique to visualize brain arteriovenous malformations (AVMs). METHODS: In this retrospective study, 15 patients (ten men and five women, mean age 44.0 ± 16.9 years) with brain AVMs were enrolled. All patients were imaged with 4D-PACK (non-selective), 4D-S-PACK, and digital subtraction angiography (DSA). Observers evaluated vessel selectivity, identification of feeding arteries and venous drainage patterns, visualization scores, and contrast-to-noise ratio (CNR) for each AVM component. Measurements were compared between the MR methods. RESULTS: Vessel selectivity was graded 4 in 43/45 (95.6%, observer 1) and 42/45 (93.3%, observer 2) territories and graded 3 in two (observer 1) and three (observer 2) territories. The sensitivity and specificity for identification of feeding arteries for both observers was 88.9% and 100% on 4D-PACK, and 100% and 100% on 4D-S-PACK, respectively. For venous drainage, the sensitivity and specificity was 100% on both methods for observer 1. The sensitivity and specificity for observer 2 was 94.4% and 83.3% on 4D-PACK, and 94.4% and 91.7% on 4D-S-PACK, respectively. The CNRs at the timepoint of 1600 ms were slightly lower in 4D-S-PACK than in 4D-PACK for all AVM components (Feeding artery, p = .02; nidus, p = .001; and draining artery, p = .02). The visualization scores for both observers were not significantly different between 4D-PACK and 4D-S-PACK for all components. CONCLUSIONS: 4D-S-PACK could be a useful non-invasive clinical tool for assessing hemodynamics in brain AVMs. KEY POINTS: • The 4D-MR angiography based on super-selective pseudo-continuous arterial spin labeling combined with CENTRA-keyhole and view-sharing (4D-S-PACK) enabled excellent vessel selectivity. • The 4D-S-PACK enabled the perfect identification of feeding arteries of brain arteriovenous malformation (AVM). • 4D-S-PACK could be a non-invasive clinical tool for assessing hemodynamics in brain AVMs.

Differentiation of high-grade from low-grade diffuse gliomas using diffusion-weighted imaging: a comparative study of mono-, bi-, and stretched-exponential diffusion models.

PURPOSE: Diffusion-weighted imaging (DWI) plays an important role in the preoperative assessment of gliomas; however, the diagnostic performance of histogram-derived parameters from mono-, bi-, and stretched-exponential DWI models in the grading of gliomas has not been fully investigated. Therefore, we compared these models' ability to differentiate between high-grade and low-grade gliomas. METHODS: This retrospective study included 22 patients with diffuse gliomas (age, 23-74 years; 12 males; 11 high-grade and 11 low-grade gliomas) who underwent preoperative 3 T-magnetic resonance imaging from October 2014 to August 2019. The apparent diffusion coefficient was calculated from the mono-exponential model. Using 13 b-values, the true-diffusion coefficient, pseudo-diffusion coefficient, and perfusion fraction were obtained from the bi-exponential model, and the distributed-diffusion coefficient and heterogeneity index were obtained from the stretched-exponential model. Region-of-interests were drawn on each imaging parameter map for subsequent histogram analyses. RESULTS: The skewness of the apparent diffusion, true-diffusion, and distributed-diffusion coefficients was significantly higher in high-grade than in low-grade gliomas (0.67 ± 0.67 vs. - 0.18 ± 0.63, 0.68 ± 0.74 vs. - 0.08 ± 0.66, 0.63 ± 0.72 vs. - 0.15 ± 0.73; P = 0.0066, 0.0192, and 0.0128, respectively). The 10th percentile of the heterogeneity index was significantly lower (0.77 ± 0.08 vs. 0.88 ± 0.04; P = 0.0004), and the 90th percentile of the perfusion fraction was significantly higher (12.64 ± 3.44 vs. 7.14 ± 1.70%: P < 0.0001), in high-grade than in low-grade gliomas. The combination of the 10th percentile of the true-diffusion coefficient and 90th percentile of the perfusion fraction showed the best area under the receiver operating characteristic curve (0.96). CONCLUSION: The bi-exponential model exhibited the best diagnostic performance for differentiating high-grade from low-grade gliomas.

A juvenile case of epilepsy-associated, isocitrate dehydrogenase wild-type/histone 3 wild-type diffuse glioma with a rare BRAF A598T mutation.

Here, we report a juvenile (18-year-old male) case of epilepsy-associated, isocitrate dehydrogenase wild-type/histone 3 wild-type diffuse glioma with a rare BRAF mutation and a focal atypical feature resembling diffuse astrocytoma. The patient presented with refractory temporal lobe epilepsy. Subsequently, magnetic resonance imaging revealed a hyperintense lesion in the right temporal lobe on fluid attenuated inversion recovery images. The patient underwent right lateral temporal lobectomy and amygdalohippocampectomy. Histopathologically, the tumor showed isomorphic, diffuse, infiltrative proliferation of glial tumor cells and intense CD34 immunoreactivity. The tumor cells were immunonegative for isocitrate dehydrogenase 1 (IDH1) R132H and BRAF V600E. Notably, the tumor cells showed the lack of nuclear staining for α-thalassemia/mental retardation syndrome, X-linked (ATRX). In addition, the Ki-67 labeling index, using a monoclonal antibody MIB-1, was elevated focally at tumor cells with p53 immunoreactivity. Molecular analyses identified a BRAFA598T mutation, the first case reported in a glioma. BRAFA598T is predicted to result in loss of kinase action; however, inactive mutants can stimulate mitogen-activated protein kinase kinase (MEK)-extracellular signal-regulated kinase (ERK) signaling through CRAF activation. Thus, according to the recent update of the consortium to inform molecular and practical approaches to central nervous system tumor taxonomy (cIMPACT-NOW update 4), our case is also compatible with diffuse glioma with the mitogen-activated protein kinase (MAPK) pathway alteration. Thorough immunohistochemical and molecular studies are necessary for diagnosis of epilepsy-associated, diffuse gliomas. Partial resemblance in histopathological and molecular genetic features to diffuse astrocytoma also calls for attention.

Acceleration-selective arterial spin labeling MR angiography for visualization of brain arteriovenous malformations.

PURPOSE: To evaluate the performance of acceleration-selective arterial spin labeling (AccASL) MR angiography in the visualization of brain arteriovenous malformations (AVMs) in comparison with digital subtraction angiography (DSA) and time-of-flight (TOF) MR angiography. METHODS: Twenty-one patients with brain AVM (mean age 31.1 ± 18.6 years; 11 males, 10 females) underwent TOF and AccASL MR angiography and DSA. Two neuroradiologists conducted an observer study for detection, nidus size, eloquence, venous drainage pattern, and Spetzler-Martin (SM) grade. The evaluations included the visualization of each AVM component with reference to DSA and assessments of contrast-to-noise ratio (CNR). The kappa statistic, repeated measures analysis of variance, Wilcoxon matched pairs test, and paired t test were used. RESULTS: Both observers detected more AVMs with AccASL (95.2%, 90.5% for Observers 1 and 2) than with TOF (76.2% and 71.4%, respectively). The inter-modality agreement between AccASL and DSA was almost perfect for the eloquence, venous drainage pattern, and SM grade for Observer 1 and moderate for the venous drainage pattern and substantial for the eloquence and SM grade for Observer 2. The visualization scores were higher with AccASL than with TOF for the feeding artery (AccASL, 4.5 ± 1.0 vs. TOF, 3.9 ± 1.5, p = 0.0214), nidus (4.6 ± 1.1 vs. 3.2 ± 1.5, p = 0.0006), and draining vein (4.6 ± 1.0 vs. 2.2 ± 1.1, p < 0.0001), respectively. The CNRs in the nidus were higher in AccASL than in TOF (29.9 ± 16.7 vs. 20.8 ± 16.5, p = 0.0002), as in the draining vein (23.2 ± 13.0 vs. 12.6 ± 12.0, p = 0.0010), respectively. CONCLUSIONS: AccASL better visualized brain AVMs compared with TOF and was useful for grading without the use of contrast agents.

Acceleration-selective Arterial Spin-labeling MR Angiography Used to Visualize Distal Cerebral Arteries and Collateral Vessels in Moyamoya Disease.

Purpose To evaluate and compare the performance of acceleration-selective arterial spin labeling (AccASL) magnetic resonance (MR) angiography in the visualization of cerebral arteries and collateral vessels in patients with Moyamoya disease with that of time-of-flight (TOF) MR angiography, with digital subtraction angiography (DSA) as the reference standard. Materials and Methods Thirty-six cerebral hemispheres from 22 patients with Moyamoya disease underwent TOF and AccASL MR angiography and DSA. Qualitative evaluations included imaging of the terminal internal carotid artery (ICA), distal middle cerebral arteries (MCAs), Moyamoya vessels, and leptomeningeal anastomosis (LMA) collaterals with reference to DSA. Quantitative evaluations included assessment of contrast-to-noise ratio (CNR) and number of vessels in MCA branches. The linear mixed-effect model was used to compare the two methods. Results Mean scores for qualitative evaluation were significantly higher with AccASL angiography than with TOF angiography for imaging distal MCAs (3.9 ± 0.3 [standard deviation] vs 2.9 ± 1.1; P < .001), Moyamoya vessels (3.6 ± 0.6 vs 2.7 ± 0.9, P < .001), and LMA collaterals (3.8 ± 0.6 vs 1.8 ± 0.7, P < .001). Scores for steno-occlusive degree around the terminal ICAs were better with TOF angiography than with AccASL angiography (2.6 ± 0.5 vs 2.4 ± 0.6, P = .023). CNRs in the M4 segment were significantly higher with AccASL angiography (11.9 ± 12.9, P < .001) than with TOF angiography (4.1 ± 7.9). The number of vessels was significantly higher with AccASL angiography (18.3 ± 5.0, P < .001) than with TOF angiography (8.9 ± 4.9). The increase in the number of vessels from TOF angiography to AccASL angiography was greater in patients with severe ICA steno-occlusion (late ICA stage group, 11.4 ± 4.5; early ICA stage group, 6.8 ± 4.0; P = .007) and well-developed leptomeningeal anastomosis (mildly developed LMA group, 7.1 ± 4.3; well-developed LMA group, 11.3 ± 4.5; P = .011). Conclusion AccASL MR angiography enables better visualization of distal cerebral arteries and collateral vessels in patients with Moyamoya disease than does TOF MR angiography, while TOF MR angiography enables better visualization of stenosis of proximal arteries. Both methods work in a mutually beneficial manner in the assessment of cerebral arteries. © RSNA, 2017 Online supplemental material is available for this article.

HLA-DRB1*04:05 allele is associated with intracortical lesions on three-dimensional double inversion recovery images in Japanese patients with multiple sclerosis.

BACKGROUND: Cortical lesions (CLs) frequently observed in Caucasian patients with multiple sclerosis (MS) contribute to disability. However, it remains unclear whether CLs are associated with clinical features and genetic risk factors, such as HLA-DRB1*15:01 and -DRB1*04:05 in Asian MS patients. OBJECTIVE: To elucidate the frequency of CLs and their association with HLA-DRB1 and DPB1 alleles in Japanese MS patients. METHODS: Three-dimensional double inversion recovery imaging and clinical information were retrospectively obtained from 92 Japanese MS patients. RESULTS: CLs of any type, intracortical lesions (ICLs), and leukocortical lesions (LCLs) were detected in 39.1%, 26.1%, and 28.3% of patients, respectively. MS patients with ICLs had a significantly higher frequency of secondary progression and greater Expanded Disability Status Scale (EDSS) scores than those without ICLs. Similar trends were observed with CLs and LCLs. The number of all three lesion types positively correlated with EDSS scores. The frequency and number of ICLs were significantly higher in HLA-DRB1*15:01 carriers than in HLA-DRB1*15:01 non-carriers, but significantly lower in HLA-DRB1*04:05 carriers than in HLA-DRB1*04:05 non-carriers. Multivariate logistic regression analysis revealed a negative association of HLA-DRB1*04:05 with ICLs. CONCLUSION: ICLs are associated with greater disease severity in Japanese MS patients and are partly suppressed by the HLA-DRB1*04:05 allele.

Diffusivity of intraorbital lymphoma vs. inflammation: comparison of single shot turbo spin echo and multishot echo planar imaging techniques.

PURPOSE: To compare the abilities of turbo spin-echo diffusion-weighted imaging (TSE DWI) and multi-shot echo planar DWI (MSh DWI) to discriminate orbital lymphoma from inflammatory lesions. MATERIALS AND METHODS: Twenty-nine patients with pathologically confirmed lymphomas and 39 patients with inflammation were imaged with a 3.0-T system. The apparent diffusion coefficient (ADC) of each lesion was measured. Signal intensities compared to normal grey matter on conventional imaging were also measured. RESULTS: The ADCs derived from the TSE DWI of the lymphomas (0.68 ± 0.14 × 10-3 mm2/s) were significantly lower than those of the inflammation cases (1.04 ± 0.39 × 10-3 mm2/s; p < 0.001). The ADCs derived from MSh DWI could not be used to separate the lymphomas from the inflammation (1.16 ± 0.43 × 10-3 mm2/s vs. 1.36 ± 0.48 × 10-3 mm2/s; p = 0.06). Conventional sequences also could not separate the lymphomas from the inflammation (p > 0.05). The ROC analysis showed the best diagnostic performance with ADCs derived from TSE DWI (the area under the curve: AUC = 0.831) followed by ADC derived from MSh DWI (AUC = 0.633). CONCLUSION: The ADCs derived from TSE DWI might help to differentiate orbital lymphomas from inflammation. KEY POINTS: • ADC of lymphoma was significantly lower than that of inflammation. • ADC derived from TSE DWI showed the best diagnostic performance. • This study was conducted by a 3-T MR scanner.