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

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

A case of Staphylococcus epidermidis osteomyelitis in the absence of spine hardware

Staphylococcus epidermidis is a typically indolent pathogen that is often considered a blood culture contaminant. It is a rare and unexpected cause of osteomyelitis, especially in the absence of recent surgical intervention or orthopedic implants. We highlight a case in which a 90-year-old Caucasian male with no recent spine surgery was found to have osteomyelitis of the lumbar spine and repeat positive blood cultures for methicillin resistant Staphylococcus epidermidis (MRSE). Further investigation revealed a history of mitral valve replacement and a new diagnosis of endocarditis leading to persistent bacteremia and seeding of his lumbar vertebrae. This case demonstrates that S. epidermidis can cause vertebral osteomyelitis resulting in severe complications that are more similar to highly pathogenic bacteria. We describe the steps to diagnosing this chronic undetected infection and related comorbidities

Arterial spin labeled perfusion MRI for the assessment of radiation-treated meningiomas

PurposeConventional contrast-enhanced MRI is currently the primary imaging technique used to evaluate radiation treatment response in meningiomas. However, newer perfusion-weighted MRI techniques, such as 3D pseudocontinuous arterial spin labeling (3D pCASL) MRI, capture physiologic information beyond the structural information provided by conventional MRI and may provide additional complementary treatment response information. The purpose of this study is to assess 3D pCASL for the evaluation of radiation-treated meningiomas.MethodsTwenty patients with meningioma treated with surgical resection followed by radiation, or by radiation alone, were included in this retrospective single-institution study. Patients were evaluated with 3D pCASL and conventional contrast-enhanced MRI before and after radiation (median follow up 6.5 months). Maximum pre- and post-radiation ASL normalized cerebral blood flow (ASL-nCBF) was measured within each meningioma and radiation-treated meningioma (or residual resected and radiated meningioma), and the contrast-enhancing area was measured for each meningioma. Wilcoxon signed-rank tests were used to compare pre- and post-radiation ASL-nCBF and pre- and post-radiation area.ResultsAll treated meningiomas demonstrated decreased ASL-nCBF following radiation (p < 0.001). Meningioma contrast-enhancing area also decreased after radiation (p = 0.008) but only for approximately half of the meningiomas (9), while half (10) remained stable. A larger effect size (Wilcoxon signed-rank effect size) was seen for ASL-nCBF measurements (r = 0.877) compared to contrast-enhanced area measurements (r = 0.597).ConclusionsASL perfusion may provide complementary treatment response information in radiation-treated meningiomas. This complementary information could aid clinical decision-making and provide an additional endpoint for clinical trials

Quantification of hemodynamics of cerebral arteriovenous malformations after stereotactic radiosurgery using 4D flow magnetic resonance imaging

Stereotactic radiosurgery (SRS) is used to treat cerebral arteriovenous malformations (AVMs). However, early evaluation of efficacy is difficult as structural magnetic resonance imaging (MRI)/magnetic resonance angiography (MRA) often does not demonstrate appreciable changes within the first 6 months. The aim of this study was to evaluate the use of four-dimensional (4D) flow MRI to quantify hemodynamic changes after SRS as early as 2 months. This was a retrospective observational study, which included 14 patients with both pre-SRS and post-SRS imaging obtained at multiple time points from 1 to 27 months after SRS. A 3T MRI Scanner was used to obtain T2 single-shot fast spin echo, time-of-flight MRA, and postcontrast 4D flow with three-dimensional velocity encoding between 150 and 200 cm/s. Post-hoc two-dimensional cross-sectional flow was measured for the dominant feeding artery, the draining vein, and the corresponding contralateral artery as a control. Measurements were performed by two independent observers, and reproducibility was assessed. Wilcoxon signed-rank tests were used to compare differences in flow, circumference, and pulsatility between the feeding artery and the contralateral artery both before and after SRS; and differences in nidus size and flow and circumference of the feeding artery and draining vein before and after SRS. Arterial flow (L/min) decreased in the primary feeding artery (mean: 0.1 ± 0.07 vs. 0.3 ± 0.2; p < 0.05) and normalized in comparison to the contralateral artery (mean: 0.1 ± 0.07 vs. 0.1 ± 0.07; p = 0.068). Flow decreased in the draining vein (mean: 0.1 ± 0.2 vs. 0.2 ± 0.2; p < 0.05), and the circumference of the draining vein also decreased (mean: 16.1 ± 8.3 vs. 15.7 ± 6.7; p < 0.05). AVM volume decreased after SRS (mean: 45.3 ± 84.8 vs. 38.1 ± 78.7; p < 0.05). However, circumference (mm) of the primary feeding artery remained similar after SRS (mean: 15.7 ± 2.7 vs. 16.1 ± 3.1; p = 0.600). 4D flow may be able to demonstrate early hemodynamic changes in AVMs treated with radiosurgery, and these changes appear to be more pronounced and occur earlier than the structural changes on standard MRI/MRA. Level of Evidence: 4 Technical Efficacy Stage: 1

Routine Repeat Head CT may not be Indicated in Patients on Anticoagulant/Antiplatelet Therapy Following Mild Traumatic Brain Injury

Introduction: Evaluation recommendations for patients on anticoagulant and antiplatelet (ACAP) therapy that present after mild traumatic brain injury (TBI) are controversial. At our institution, an initial noncontrast head computed tomography (HCT) is performed, with a subsequent HCT performed six hours later to exclude delayed intracranial hemorrhage (ICH). This study was performed to evaluate the yield and advisability of this approach.Methods: We performed a retrospective review of subjects undergoing evaluation for ICH after mild TBI in patients on ACAP therapy between January of 2012 and April of 2013. We assessed for the frequency of ICH on both the initial noncontrast HCT and on the routine six-hour follow-up HCT. Additionally, chart review was performed to evaluate the clinical implications of ICH, when present, and to interrogate whether pertinent clinical and laboratory data may predict the presence of ICH prior to imaging. We used multivariate generalized linear models to assess whether presenting Glasgow Coma Score (GCS), loss of consciousness (LOC), neurological or physical examination findings, international normalized ratio, prothrombin time, partial thromboplastin time, platelet count, or specific ACAP regimen predicted ICH.Results: 144 patients satisfied inclusion criteria. Ten patients demonstrated initial HCT positive for ICH, with only one demonstrating delayed ICH on the six-hour follow-up HCT. This patient was discharged without any intervention required or functional impairment. Presenting GCS deviation (p<0.001), LOC (p=0.04), neurological examination findings (p<0.001), clopidogrel (p=0.003), aspirin (p=0.03) or combination regimen (p=0.004) use were more commonly seen in patients with ICH.Conclusion: Routine six-hour follow-up HCT is likely not indicated in patients on ACAP therapy, as our study suggests clinically significant delayed ICH does not occur. Additionally, presenting GCS deviation, LOC, neurological examination findings, clopidogrel, aspirin or combination regimen use may predict ICH, and, in the absence of these findings, HCT may potentially be forgone altogether. [West J Emerg Med. 2015;16(1):-0.

Bevacizumab: radiation combination produces restricted diffusion on brain MRI.

AimsThe purpose of this paper is to investigate the effect of bevacizumab (BEV) on the diffusion properties of irradiated brain gliomas.Materials & methodsNeuroimaging studies and medical records of 44 patients undergoing treatment for cerebral gliomas were reviewed. MRIs were analyzed for presence of restricted diffusion, time to onset, pattern/location, duration of restriction, and persistence of restriction post-treatment with BEV.ResultsPatchy confluent areas of diffusion restriction on MRI were found in 12 patients. All 12 patients received radiation therapy followed by BEV therapy. Diffusion restriction appeared 3 to 21 months after onset of radiation and 1 to 6 months after starting BEV therapy, increased in size over time, and persisted up to 23 months while on BEV. Restricted diffusion was observed in areas that received 60 Gy or more of radiation. Areas of restricted diffusion showed low T1 and increased T2 signal intensity, minimal or no contrast enhancement, and low cerebral blood volume. A thin perimeter of susceptibility outlined the restricted areas on susceptibility-weighted images in nine patients (75%). Small focal areas of tumor recurrence within larger regions of restricted diffusion were evident in only four patients (33%). In seven patients (58%) the area of restricted diffusion showed necrosis or radiation change on histology or no metabolic activity on MR spectroscopy or PET.ConclusionRestricted diffusion associated with BEV-treated cerebral gliomas occurs in regions of high-dose radiation and does not indicate high-cellularity of tumor recurrence

Diagnostic utility of restriction spectrum imaging (RSI) in glioblastoma patients after concurrent radiation-temozolomide treatment: A pilot study.

Discriminating between tumor recurrence and treatment effects in glioblastoma patients undergoing radiation-temozolomide (RT/TMZ) therapy remains a major clinical challenge. Here, we report a pilot study to determine the utility of restriction spectrum imaging (RSI), an advanced diffusion-weighted MRI (DWI) technique that affords meso-scale resolution of cell density, in this assessment. A retrospective review of 31 patients with glioblastoma treated between 2011 and 2017 who underwent surgical resection or biopsy over radiographic concern for tumor recurrence following RT/TMZ was performed. All patients underwent RSI prior to surgical resection. Diagnostic utility of RSI for tumor recurrence was determined in comparison to histopathology. Analysis of surgical specimens revealed treatment effects in 6/31 patients (19%) and tumor recurrence in 25/31 patients (81%). There was general concordance between the measured RSI signal and histopathologic diagnosis. RSI was negative in 5/6 patients (83%) in patients with histological evidence of treatment effects. RSI was positive in 21/25 patients (84%) in patients with tumor recurrence. The sensitivity, specificity, positive and negative predictive values of RSI for glioblastoma recurrence were 84%, 86%, 95%, and 60%, respectively. Histopathologic review showed agreement between the RSI signal and cellularity of the tumor specimen. These data support the use of RSI in the evaluation of treatment effects versus tumor recurrence in glioblastoma patients after RT-TMZ therapy