Case report: Neuronal intranuclear inclusion disease presenting with acute encephalopathy.

Neuronal intranuclear inclusion disease (NIID), a neurodegenerative disease previously thought to be rare, is increasingly recognized despite heterogeneous clinical presentations. NIID is pathologically characterized by ubiquitin and p-62 positive intranuclear eosinophilic inclusions that affect multiple organ systems, including the brain, skin, and other tissues. Although the diagnosis of NIID is challenging due to phenotypic heterogeneity, a greater understanding of the clinical and imaging presentations can improve accurate and early diagnosis. Here, we present three cases of pathologically proven adult-onset NIID, all presenting with episodes of acute encephalopathy with protracted workups and lengthy time between symptom onset and diagnosis. Case 1 highlights challenges in the diagnosis of NIID when MRI does not reveal classic abnormalities and provides a striking example of hyperperfusion in the setting of acute encephalopathy, as well as unique pathology with neuronal central chromatolysis, which has not been previously described. Case 2 highlights the progression of MRI findings associated with multiple NIID-related encephalopathic episodes over an extended time period, as well as the utility of skin biopsy for antemortem diagnosis.

The diagnostic value of susceptibility-weighted imaging for identifying acute intraarticular hemorrhages.

PURPOSE: To evaluate the diagnostic performance of susceptibility-weighted imaging (SWI) in identifying acute intraarticular hemorrhages and differentiating blood from other types of joint effusions. METHODS: Thirty-two patients (21 men, 11 women; mean age 38.7 ± 16.5 SD) clinically suspected of having joint effusion were prospectively included. All the patients underwent both conventional MRI and SWI. Two radiologists independently reviewed the conventional MRI images and scored the likelihood of intraarticular hemorrhage using a 5-level scoring system. Immediately thereafter, SWI images of each patient were also provided for the radiologists, and the scoring was repeated evaluating the conventional MRI and SWI images together. The patients underwent joint aspiration or surgical operation as the reference standard. The area under the curve (AUC) of conventional MRI and conventional MRI + SWI methods were calculated and compared. The weighted kappa analysis was used to evaluate the interobserver agreement. RESULTS: Traumatic knee injury comprised the majority of study sample. Eighteen out of 32 of the patients were proven to have intraarticular hemorrhage. Using the conventional MRI, reader 1 and 2 achieved AUCs of 0.67 (p = 0.09) and 0.53 (p = 0.76), respectively. Following the addition of SWI, reader 1 and 2 achieved AUCs of 0.96 (p = 0.0001) and 0.95 (p = 0.0001), respectively, and interobserver agreement improved from Κ = 0.61 to Κ = 0.93. Accordingly, difference between the AUCs was 0.28 (p = 0.003) and 0.42 (p = 0.0001) for reader 1 and 2, respectively. CONCLUSIONS: If confirmed by future studies, SWI enables the reliable and accurate diagnosis of acute intraarticular hemorrhages.

Fibrodysplasia ossificans progressiva (FOP) presenting as a rapidly growing non-calcified neck mass.

Fibrodysplasia ossificans progressiva (FOP) is an extremely rare autosomal dominant inherited disorder leading to mature ossification within soft tissues. We report a 62-year-old female with a 3-week history of a rapidly enlarging left neck mass with no associated symptoms. A neck CT showed a ~10 cm solid-appearing non-calcified left neck mass that markedly decreased in size on a one-month follow-up neck MRI, but with new extensive edema/intense enhancement in floor of the mouth. Prior radiographs documented hallux valgus and heterotopic ossification of the psoas/paraspinal muscles and shoulder girdle. In this case of FOP, no intervention was implemented and the symptoms improved over time and thus paralleled other such cases for flare-ups. Clinicians should be aware of this rare entity, as it is frequently misdiagnosed as cancer or other benign entities such as infection, resulting in biopsies that can often hasten disease progression.

ADC, D, f dataset calculated through the simplified IVIM model, with MGMT promoter methylation, age, and ECOG, in 38 patients with wildtype IDH glioblastoma.

Patients undergoing standard chemoradiation post-resection had MRIs at radiation planning and fractions 10 and 20 of chemoradiation. MRIs were 1.5T and 3D T2-FLAIR, pre- and post-contrast 3D T1-weighted (T1) and echo planar DWI with three b-values (0, 500, and 1000s/mm2) were acquired. T2-FLAIR was coregistered to T1C images. Non-overlapping T1 contrast-enhancing (T1C) and nonenhancing T2-FLAIR hyperintense regions were segmented, with necrotic/cystic regions, the surgical cavity, and large vessels excluded. The simplified IVIM model was used to calculate voxelwise diffusion coefficient (D) and perfusion fraction (f) maps; ADC was calculated using the natural logarithm of b = 1000 over b = 0 images. T1C and T2-FLAIR segmentations were brought into this space, and medians calculated. MGMT promoter methylation status (MGMTPMS), age at diagnosis, and Eastern Cooperative Oncology Group (ECOG) performance status were extracted from electronic medical records. The data were presented, analyzed, and described in the article, "Intravoxel incoherent motion (IVIM) modeling of diffusion MRI during chemoradiation predicts therapeutic response in IDH wildtype Glioblastoma", published in Radiotherapy and Oncology [1].

Intravoxel incoherent motion (IVIM) modeling of diffusion MRI during chemoradiation predicts therapeutic response in IDH wildtype glioblastoma.

BACKGROUND: Prediction of early progression in glioblastoma may provide an opportunity to personalize treatment. Simplified intravoxel incoherent motion (IVIM) MRI offers quantitative estimates of diffusion and perfusion metrics. We investigated whether these metrics, during chemoradiation, could predict treatment outcome. METHODS: 38 patients with newly diagnosed IDH-wildtype glioblastoma undergoing 6-week/30-fraction chemoradiation had standardized post-operative MRIs at baseline (radiation planning), and at the 10th and 20th fractions. Non-overlapping T1-enhancing (T1C) and non-enhancing T2-FLAIR hyperintense regions were independently segmented. Apparent diffusion coefficient (ADCT1C, ADCT2-FLAIR) and perfusion fraction (fT1C, fT2-FLAIR) maps were generated with simplified IVIM modelling. Parameters associated with progression before or after 6.9 months (early vs late progression, respectively), overall survival (OS) and progression-free survival (PFS) were investigated. RESULTS: Higher ADCT2-FLAIR at baseline [Odds Ratio (OR) = 1.06, 95% CI 1.01-1.15, p = 0.025], lower fT2-FLAIR at fraction 10 (OR = 2.11, 95% CI 1.04-4.27, p = 0.018), and lack of increase in ADCT2-FLAIR at fraction 20 compared to baseline (OR = 1.12, 95% CI 1.02-1.22, p = 0.02) were associated with early progression. Combining ADCT2-FLAIR at baseline, fT2-FLAIR at fraction 10, ECOG and MGMT promoter methylation status significantly improved AUC to 90.3% compared to a model with only ECOG and MGMT promoter methylation status (p = 0.001). Using multivariable analysis, neither IVIM metrics were associated with OS but higher fT2-FLAIR at fraction 10 (HR = 0.72, 95% CI 0.56-0.95, p = 0.018) was associated with longer PFS. CONCLUSION: ADCT2-FLAIR at baseline, its lack of increase from baseline to fraction 20, or fT2-FLAIR at fraction 10 significantly predicted early progression. fT2-FLAIR at fraction 10 was associated with PFS.

Quantitative CEST and MT at 1.5T for monitoring treatment response in glioblastoma: early and late tumor progression during chemoradiation.

PURPOSE: Quantitative MRI (qMRI) was performed using a 1.5T protocol that includes a novel chemical exchange saturation transfer/magnetization transfer (CEST/MT) approach. The purpose of this prospective study was to determine if qMRI metrics at baseline, at the 10th and 20th fraction during a 30 fraction/6 week standard chemoradiation (CRT) schedule, and at 1 month following treatment could be an early indicator of response for glioblastoma (GBM). METHODS: The study included 51 newly diagnosed GBM patients. Four regions-of-interest (ROI) were analyzed: (i) the radiation defined clinical target volume (CTV), (ii) radiation defined gross tumor volume (GTV), (iii) enhancing-tumor regions, and (iv) FLAIR-hyperintense regions. Quantitative CEST, MT, T1 and T2 parameters were compared between those patients progressing within 6.9 months (early), and those progressing after CRT (late), using mixed modelling. Exploratory predictive modelling was performed to identify significant predictors of early progression using a multivariable LASSO model. RESULTS: Results were dependent on the specific tumor ROI analyzed and the imaging time point. The baseline CEST asymmetry within the CTV was significantly higher in the early progression cohort. Other significant predictors included the T2 of the MT pools (for semi-solid at fraction 20 and water at 1 month after CRT), the exchange rate (at fraction 20) and the MGMT methylation status. CONCLUSIONS: We observe the potential for multiparametric qMRI, including a novel pulsed CEST/MT approach, to show potential in distinguishing early from late progression GBM cohorts. Ultimately, the goal is to personalize therapeutic decisions and treatment adaptation based on non-invasive imaging-based biomarkers.

Accuracy of diffusion-weighted imaging in discriminating atypical vertebral haemangiomas from malignant masses in patients with vertebral lesions: a cross-sectional study.

PURPOSE: Vertebral haemangiomas are incidental findings in imaging modalities. Atypical haemangiomas are haeman-giomas rich in vascular tissue, and they are found to be hypointense in T1 sequences and hyperintense in T2 sequences, mimicking the findings of metastatic lesions. In the present study we aim to evaluate the ability of diffusion- weighted imaging to differentiate these two groups of vertebral lesions. MATERIAL AND METHODS: In the present cross-sectional study, a total of 23 lesions were included, including 10 haemangiomas and 13 malignant lesions. Diffusion-weighted imaging was used to compare atypical haemangiomas and metastatic lesions. The apparent diffusion co-efficient was determined for each lesion, and then the mean of each group was calculated. The means were then compared. Receiver operating characteristic analysis was used to determine a cut-off ADC value to differentiate these lesions. RESULTS: The difference between the mean age of the two groups was not significant. The mean ADC value for atypical haemangiomas was 1884 ± 74 × 10-6 mm2/s and 1008 ± 81 × 10-6 mm2/s for the malignant lesions. The difference between the two groups was statistically significant (p < 10-3). ROC curve analysis determined an ADC value of 958 × 10-6 mm2/s to be able to differentiate between atypical haemangiomas and malignant lesions. CONCLUSIONS: Diffusion-weighted MRI could be used to differentiate between atypical haemangiomas and malignant metastatic lesions.

Differentiation of progressive disease from pseudoprogression using 3D PCASL and DSC perfusion MRI in patients with glioblastoma.

PURPOSE: To use 3D pseudocontinuous arterial spin labeling (3D PCASL) and dynamic susceptibility contrast-enhanced (DSC) perfusion MRI to differentiate progressive disease from pseudoprogression in patients with glioblastoma (GBM). METHODS: Thirty-two patients with GBM who developed progressively enhancing lesions within the radiation field following resection and chemoradiation were included in this retrospective, single-institution study. The updated modified RANO criteria were used to establish progressive disease or pseudoprogression. Following 3D PCASL and DSC MR imaging, perfusion parameter estimates of cerebral blood flow (ASL-nCBF and DSC-nrCBF) and cerebral blood volume (DSC-nrCBV) were calculated. Additionally, contrast enhanced volumes were measured. Mann-Whitney U tests were used to compare groups. Linear discriminant analysis (LDA) and area under receiver operator characteristic curve (AUC) analyses were used to evaluate performance of each perfusion parameter and to determine optimal cut-off points. RESULTS: All perfusion parameter measurements were higher in patients with progressive disease (mean, 95% CI ASL-nCBF 2.48, [2.03, 2.93]; DSC-nrCBF = 2.27, [1.85, 2.69]; DSC-nrCBV = 3.51, [2.37, 4.66]) compared to pseudoprogression (mean, 95% CI ASL-nCBF 0.99, [0.47, 1.52]; DSC-nrCBF = 1.05, [0.36, 1.74]; DSC-nCBV = 1.19, [0.34, 2.05]), and findings were significant at the p < 0.0125 level (p = 0.001, 0.003, 0.002; effect size: Cohen's d = 1.48, 1.27, and 0.92). Contrast enhanced volumes were not significantly different between groups (p > 0.447). All perfusion parameters demonstrated high AUC (0.954 for ASL-nCBF, 0.867 for DSC-nrCBF, and 0.891 for DSC-nrCBV), however, ASL-nCBF demonstrated the highest AUC and misclassified the fewest cases (N = 6). Lesions correctly classified by ASL but misclassified by DSC were located along the skull base or adjacent to large resection cavities with residual blood products, at areas of increased susceptibility. CONCLUSION: Both 3D PCASL and DSC perfusion MRI techniques have nearly equivalent performance for the differentiation of progressive disease from pseudoprogression in patients with GBM. However, 3D PCASL is less sensitive to susceptibility artifact and may allow for improved classification in select cases.

Clinical and histopathological outcome of cervical and chest MRI involving non-MRI-conditional cardiac pacemakers: a study using sheep models.

AIM: To examine the clinical and histopathological consequences of MRI in sheep implanted with non-MRI-conditional cardiac pacemakers. MATERIALS AND METHODS: Under general anesthesia, active fixation leads of two dual-chamber, non-MRI-conditional cardiac pacemakers (St. Jude Medical and Medtronic) were implanted either at the right ventricular apex or at the right atrium of two male sheep and connected to the V and A channels of the pacemakers, respectively. The generators were placed in cervical subcutaneous pockets. On day 5, both sheep underwent 1.5 T cervical and chest MRI with continuous electrocardiogram monitoring. Obtained sequences were T1-weighted (T1W), T2-weighted (T2W), T2-gradient echo and diffusion weighted (DW). The employed modes were OVO, VOO and VVI for one sheep and OAO, AOO and AAI for the other (unipolar and bipolar configuration of pacing and sensing for both). Battery impedance, pacing lead impedance, intrinsic amplitude and capture thresholds were checked at baseline and after each sequence, as well as 48 h after imaging. Histopathological examination of the cardiac tissue around the lead tip was performed 4 weeks post-imaging. RESULTS: No significant changes in device position or configuration were observed during or after MRI. Clinical outcome was uneventful in both sheep. Minor inflammatory and necrotic changes were reported after histopathological examination of the cardiac tissue around the lead tip. CONCLUSION: 1.5 T MRI of two implanted non-MRI-conditional pacemakers was found safe in terms of device configuration and stability, clinical outcome and cardiac tissue histopathological findings.

Restriction Spectrum Imaging Differentiates True Tumor Progression From Immune-Mediated Pseudoprogression: Case Report of a Patient With Glioblastoma.

Immunotherapy is increasingly used in the treatment of glioblastoma (GBM), with immune checkpoint therapy gaining in popularity given favorable outcomes achieved for other tumors. However, immune-mediated (IM)-pseudoprogression is common, remains poorly characterized, and renders conventional imaging of little utility when evaluating for treatment response. We present the case of a 64-year-old man with GBM who developed pathologically proven IM-pseudoprogression after initiation of a checkpoint inhibitor, and who subsequently developed true tumor progression at a distant location. Based on both qualitative and quantitative analysis, we demonstrate that an advanced diffusion-weighted imaging (DWI) technique called restriction spectrum imaging (RSI) can differentiate IM-pseudoprogression from true progression even when conventional imaging, including standard DWI/apparent diffusion coefficient (ADC), is not informative. These data complement existing literature supporting the ability of RSI to estimate tumor cellularity, which may help to resolve complex diagnostic challenges such as the identification of IM-pseudoprogression.

Qualitative Posttreatment Diffusion-Weighted Imaging as a Predictor of 90-day Outcome in Stroke Intervention.

PURPOSE: The aim was to assess the ability of post-treatment diffusion-weighted imaging (DWI) to predict 90-day functional outcome in patients with endovascular therapy (EVT) for large vessel occlusion in acute ischemic stroke (AIS). METHODS: We examined a retrospective cohort from March 2016 to January 2018, of consecutive patients with AIS who received EVT. Planimetric DWI was obtained and infarct volume calculated. Four blinded readers were asked to predict modified Rankin Score (mRS) at 90 days post-thrombectomy. RESULTS: Fifty-one patients received endovascular treatment (mean age 65.1 years, median National Institutes of Health Stroke Scale (NIHSS) 18). Mean infarct volume was 43.7 mL. The baseline NIHSS, 24-hour NIHSS, and the DWI volume were lower for the mRS 0-2 group. Also, the thrombolysis in cerebral infarction (TICI) 2b/3 rate was higher in the mRS 0-2 group. No differences were found in terms of the occlusion level, reperfusion technique, or recombinant tissue plasminogen activator use. There was a significant association noted between average infarct volume and mRS at 90 days. On multivariable analysis, higher infarct volume was significantly associated with 90-day mRS 3-5 when adjusted to TICI scores and occlusion location (OR 1.01; CI 95% 1.001-1.03; p = 0.008). Area under curve analysis showed poor performance of DWI volume reader ability to qualitatively predict 90-day mRS. CONCLUSION: The subjective impression of DWI as a predictor of clinical outcome is poorly correlated when controlling for premorbid status and other confounders. Qualitative DWI by experienced readers both overestimated the severity of stroke for patients who achieved good recovery and underestimated the mRS for poor outcome patients. Infarct core quantitation was reliable.

The Effect of Females' Reproductive Factors on Pituitary Gland Size in Women at Reproductive Age.

Background and Objectives: The brain imaging of the pituitary gland in females has shown a change in pituitary size and volume in the female's population. It has been proven that the pituitary gland is affected by pregnancy, giving birth, and hormone-related factors. Therefore, this study aimed to evaluate the factors which may have an impact on the pituitary size in females at reproductive age and compare the pituitary size in females with a history of pregnancy, those at the postpartum period, and nullipara females. Materials and Methods: This population-based study was conducted on 208 healthy women aged 12-55 years old. Participants underwent cranial Magnetic resonance imaging (MRI), and pituitary diameters (craniocaudal, anteroposterior, and transverse) and volume were measured for each subject. The correlation of age, gravity, parity, lactation, and intake of oral contraceptives with pituitary size were analyzed. Results: One-hundred and eighty females met the criteria for participation. The pituitary volume correlated negatively with hormone-related factors. The gravity (r = -0.35) and parity (r = -0.35) had significant negative effects on the pituitary volume (p < 0.001). The use of oral contraceptives and lactation were also in negative correlation with the pituitary volume (r = -0.20, p = 0.006, r = -0.56, p < 0.001, respectively). The craniocaudal diameter was also affected by gravity (r = -0.62), parity (r = -0.57), intake of contraceptives (r = -0.32), and lactation (r = -0.70), p < 0.001. The anteroposterior diameter of the pituitary gland associated significantly with gravity (r = -0.19, p = 0.009), parity (r = -0.20, p = 0.007), and lactation (r = -0.25, p = 0.001). The transverse diameter of the pituitary gland also related negatively with reproductive factors such as gravity (r = -0.15, p = 0.04), parity (r = -0.17, p = 0.02), and lactation (r = -0.17, p = 0.02). The pituitary gland of nullipara females was the greatest in size. Recent pregnancy led to increased craniocaudal and anteroposterior diameters. Conclusions: In this study, we found a negative effect of pregnancy and giving birth on pituitary size. Nullipara females were found to have the greatest pituitaries, even greater than the females in the postpartum period.

Effect of progesterone administration on prognosis of patients with diffuse axonal injury due to severe head trauma.

OBJECTIVE: Severe traumatic brain injury (TBI) has a major role in mortality rate among the other types of trauma. The aim of this clinical study was to assess the effect of progesterone on the improvement of neurologic outcome in patients with acute severe TBI. METHODS: A total of 76 patients who had arrived within 8h of injury with a Glasgow Coma Score≤8 were enrolled in the study. In a randomized style 38 received progesterone (1mg/kg per 12h for 5 days) and 38 did not. RESULTS: There was a better recovery rate and GOS score for the patients who were given progesterone than for those in the control group in a 3-months follow-up period (50% vs. 21%); subgroup analysis showed a significant difference in the percentage of favorable outcome between the two groups with GCS of 5-8 (p=0.03). CONCLUSION: The use of progesterone may significantly improve neurologic outcome of patients suffering severe TBI up to 3 months after injury, especially those with 5≤GCS≤8, providing a potential benefit to the treatment of acute severe TBI patients. Considering this drug had no significant side effects, so progesterone could be used in patients with severe TBI as a neuro-protective drug.

Extramedullary plasmacytoma presenting as a solitary mass in the intracranial posterior fossa.

A patient with a 3-month history of headache refractory to pain medication was admitted. The CT scan and MRI showed evidence of a posterior fossa mass. This was pathologically confirmed as an extra medullary plasmacytoma (EMP). He had a pathologic fracture of the left humerus 7 years ago while the radiologist was unaware at the time of diagnosis. A solitary bone plasmacytoma (SBP) was the cause of the pathologic fracture. This report includes the first description of MRI findings in a patient with a rare-incidence intracranial solitary extra medullary plasmacytoma (SEP) in Iran. There is a striking similarity between the features of intracranial SEP and meningiomas. Intracranial SEP, although rare, should be included in the differential diagnosis of brain tumors in areas where meningiomas commonly arise. The MRI findings and differential diagnosis of plasmacytoma are reviewed. Before this case report, only few cases have been reported in the literature. Nonetheless, this is the first report of posterior fossa EMP from Iran.