Izlem Izbudak

Dynamic Imaging of Allogeneic Mesenchymal Stem Cells Trafficking to Myocardial Infarction

Background—Recent results from animal studies suggest that stem cells may be able to home to sites of myocardial injury to assist in tissue regeneration. However, the histological interpretation of postmortem tissue, on which many of these studies are based, has recently been widely debated. Methods and Results—With the use of the high sensitivity of a combined single-photon emission CT (SPECT)/CT scanner, the in vivo trafficking of allogeneic mesenchymal stem cells (MSCs) colabeled with a radiotracer and MR contrast agent to acute myocardial infarction was dynamically determined. Redistribution of the labeled MSCs after intravenous injection from initial localization in the lungs to nontarget organs such as the liver, kidney, and spleen was observed within 24 to 48 hours after injection. Focal and diffuse uptake of MSCs in the infarcted myocardium was already visible in SPECT/CT images in the first 24 hours after injection and persisted until 7 days after injection and was validated by tissue counts of radioactivity. In contrast, MRI was unable to demonstrate targeted cardiac localization of MSCs in part because of the lower sensitivity of MRI. Conclusions—Noninvasive radionuclide imaging is well suited to dynamically track the biodistribution and trafficking of mesenchymal stem cells to both target and nontarget organs.

MR-trackable intramyocardial injection catheter

There is growing interest in delivering cellular agents to infarcted myocardium to prevent postinfarction left ventricular remodeling. MRI can be effectively used to differentiate infarcted from healthy myocardium. MR‐guided delivery of cellular agents/therapeutics is appealing because the therapeutics can be precisely targeted to the desired location within the infarct. In this study, a steerable intramyocardial injection catheter that can be actively tracked under MRI was developed and tested. The components of the catheter were arranged to form a loopless RF antenna receiver coil that enabled active tracking. Feasibility studies were performed in canine and porcine myocardial infarction models. Myocardial delayed‐enhancement (MDE) imaging identified the infarcted myocardium, and real‐time MRI was used to guide left ventricular catheterization from a carotid artery approach. The distal 35 cm of the catheter was seen under MRI with a bright signal at the distal tip of the catheter. The catheter was steered into position, the distal tip was apposed against the infarct, the needle was advanced, and a bolus of MR contrast agent and tissue marker dye was injected intramyocardially, as confirmed by imaging and postmortem histology. A pilot study involving intramyocardial delivery of magnetically labeled stem cells demonstrated the utility of the active injection catheter system. Magn Reson Med 51:1163–1172, 2004.

Association of Cortical Lesion Burden on 7-T Magnetic Resonance Imaging With Cognition and Disability in Multiple Sclerosis

IMPORTANCE Cortical lesions (CLs) contribute to physical and cognitive disability in multiple sclerosis (MS). Accurate methods for visualization of CLs are necessary for future clinical studies and therapeutic trials in MS. OBJECTIVE To evaluate the clinical relevance of measures of CL burden derived from high-field magnetic resonance imaging (MRI) in MS. DESIGN, SETTING, AND PARTICIPANTS An observational clinical imaging study was conducted at an academic MS center. Participants included 36 individuals with MS (30 relapsing-remitting, 6 secondary or primary progressive) and 15 healthy individuals serving as controls. The study was conducted from March 10, 2010, to November 23, 2012, and analysis was performed from June 1, 2011, to September 30, 2014. Seven-Tesla MRI of the brain was performed with 0.5-mm isotropic resolution magnetization-prepared rapid acquisition gradient echo (MPRAGE) and whole-brain, 3-dimensional, 1.0-mm isotropic resolution magnetization-prepared, fluid-attenuated inversion recovery (MPFLAIR). Cortical lesions, seen as hypointensities on MPRAGE, were manually segmented. Lesions were classified as leukocortical, intracortical, or subpial. Images were segmented using the Lesion-TOADS (Topology-Preserving Anatomical Segmentation) algorithm, and brain structure volumes and white matter (WM) lesion volume were reported. Volumes were normalized to intracranial volume. MAIN OUTCOMES AND MEASURES Physical disability was measured by the Expanded Disability Status Scale (EDSS). Cognitive disability was measured with the Minimal Assessment of Cognitive Function in MS battery. RESULTS Cortical lesions were noted in 35 of 36 participants (97%), with a median of 16 lesions per participant (range, 0-99). Leukocortical lesion volume correlated with WM lesion volume (ρ = 0.50; P = .003) but not with cortical volume; subpial lesion volume inversely correlated with cortical volume (ρ = -0.36; P = .04) but not with WM lesion volume. Total CL count and volume, measured as median (range), were significantly increased in participants with EDSS scores of 5.0 or more vs those with scores less than 5.0 (count: 29 [11-99] vs 13 [0-51]; volume: 2.81 × 10-4 [1.30 × 10-4 to 7.90 × 10-4] vs 1.50 × 10-4 [0 to 1.01 × 10-3]) and in cognitively impaired vs unimpaired individuals (count: 21 [0-99] vs 13 [1-54]; volume: 3.51 × 10-4 [0 to 1.01 × 10-4] vs 1.19 × 10-4 [0 to 7.17 × 10-4]). Cortical lesion volume correlated with EDSS scores more robustly than did WM lesion volume (ρ = 0.59 vs 0.36). Increasing log[CL volume] conferred a 3-fold increase in the odds of cognitive impairment (odds ratio [OR], 3.36; 95% CI, 1.07-10.59; P = .04) after adjustment for age and sex and a 14-fold increase in odds after adjustment for WM lesion volume and atrophy (OR, 14.26; 95% CI, 1.06-192.37; P = .045). Leukocortical lesions had the greatest effect on cognition (OR for log [leukocortical lesion volume], 9.65; 95% CI, 1.70-54.59, P = .01). CONCLUSIONS AND RELEVANCE This study provides in vivo evidence that CLs are associated with cognitive and physical disability in MS and that leukocortical and subpial lesion subtypes have differing clinical relevance. Quantitative assessments of CL burden on high-field MRI may further our understanding of the development of disability and progression in MS and lead to more effective treatments.

Medulloblastoma: atypical CT and MRI findings in children

Posterior fossa mass lesions in children usually present a diagnostic challenge despite their high frequency and the limited number of differential diagnostic possibilities. Consideration of medulloblastoma within the differential diagnosis of such lesions mandates an aggressive surgical approach as residual tumor is a known risk factor for poor prognosis. Preoperative imaging of the entire neuroaxis is critical given the high propensity of drop metastases. In this pictorial presentation, we review and demonstrate less common features of medulloblastomas to facilitate diagnosis in challenging cases.

The many faces of fungal disease of the paranasal sinuses: CT and MRI findings.

The prevalence of fungal rhinosinusitis has increased worldwide over the last two decades. Fungal rhinosinusitis includes a wide variety of infections, from relatively innocent to rapidly fatal processes. Fungal infection may be one of the most challenging forms of sinonasal pathology to manage, especially the invasive forms, which have high mortality rates. Therefore, it is essential to correctly diagnose and classify fungal disease of paranasal sinuses in order to accurately predict prognosis and implement effective therapy. This essay describes the different manifestations of fungal sinusitis on computed tomography and magnetic resonance imaging to optimize differentiation, and includes correlation with the pathologic classifications.

Differentiating neuromyelitis optica from other causes of longitudinally extensive transverse myelitis on spinal magnetic resonance imaging

Background: Although spinal magnetic resonance imaging (MRI) findings of neuromyelitis optica (NMO) have been described, there is limited data available that help differentiate NMO from other causes of longitudinally extensive transverse myelitis (LETM). Objective: To investigate the spinal MRI findings of LETM that help differentiate NMO at the acute stage from multiple sclerosis (MS) and other causes of LETM. Methods: We enrolled 94 patients with LETM into our study. Bright spotty lesions (BSL), the lesion distribution and location were evaluated on axial T2-weighted images. Brainstem extension, cord expansion, T1 darkness and lesion enhancement were noted. We also reviewed the brain MRI of the patients during LETM. Results: Patients with NMO had a greater amount of BSL and T1 dark lesions (p < 0.001 and 0.003, respectively). The lesions in NMO patients were more likely to involve greater than one-half of the spinal cord’s cross-sectional area; to enhance and be centrally-located, or both centrally- and peripherally-located in the cord. Of the 62 available brain MRIs, 14 of the 27 whom were NMO patients had findings that may be specific to NMO. Conclusions: Certain spinal cord MRI features are more commonly seen in NMO patients and so obtaining brain MRI during LETM may support diagnosis.

Delayed posthypoxic leukoencephalopathy: a case series and review of the literature.

Delayed posthypoxic leukoencephalopathy (DPHL) is a rare and underrecognized entity where patients manifest a neurological relapse after initial recovery from an acute hypoxic episode. We sought to describe the magnetic resonance imaging (MRI) findings in a group of patients with DPHL and review the available literature.

Longitudinally extensive optic neuritis as an MRI biomarker distinguishes neuromyelitis optica from multiple sclerosis.

OBJECTIVE To differentiate MRI characteristics of optic neuritis associated with neuromyelitis optica (NMO) and relapsing remitting multiple sclerosis (RRMS). BACKGROUND Optic neuritis is a common presenting feature of both neuromyelitis optica and multiple sclerosis. Distinguishing between NMO and RRMS is important in guiding treatment, but biomarkers of NMO and MS can be absent early in the disease process. We looked for differences in MRI characteristics of optic neuritis associated with NMO and MS that provide an early clue in the diagnostic workup. DESIGN/METHODS We conducted a retrospective analysis of 26 NMO and 26 RRMS patients presenting to the Johns Hopkins Hospital with MRI-confirmed acute optic neuritis. MRIs were assessed to identify the location and longitudinal extent of each contrast enhancing lesion. For the purposes of this study, the optic nerve was divided into intraorbital, canalicular, pre-chiasmal, chiasmal, and optic tract. RESULTS There are distinct differences in MRI characteristics between NMO- and RRMS-associated optic neuritis. The majority of NMO lesions were longitudinally extensive measuring at least 17.6mm in length and involving at least three optic nerve segments. At a cutoff of 17.6mm lesion length, the specificity for NMO is 76.9% with a sensitivity of 80.8% and positive likelihood ratio of 3.50. Conversely, MS lesions were more commonly focal in one optic nerve segment localized anteriorly. CONCLUSIONS Optic neuritis in NMO has a distinct pattern on MRI as compared with RRMS and can help differentiate these two neuroinflammatory diseases at presentation.

Accuracy of head ultrasound for the detection of intracranial hemorrhage in preterm neonates: comparison with brain MRI and susceptibility-weighted imaging.

OBJECTIVES To evaluate the sensitivity and specificity of head ultrasound (HUS) in the detection of intracranial hemorrhage in premature neonates compared with brain MRI using susceptibility-weighted imaging (SWI). MATERIAL AND METHODS Ultrasound (US) and MRI scans of the brain using SWI in premature neonates were retrospectively evaluated for grade I-III germinal matrix hemorrhage (GMH), periventricular hemorrhagic infarction (PVHI), intra-axial hemorrhage other than PVHI, extra-axial hemorrhage in each cerebral hemisphere and cerebellar hemorrhage in each cerebellar hemisphere. The impact of these hemorrhagic findings on short-term clinical management was also reviewed. RESULTS Twelve neonates (mean age: 9.8 days; range: 3-23 days) with a mean gestational age of 32.8 weeks (range: 29.6-35.4 weeks) were included in the study. HUS had high sensitivity (100%) and specificity (93.3%) in detecting grade III GMH using SWI as a reference, but poor sensitivity (0%) in the detection of intraventricular hemorrhage with normal-sized ventricles (grade II GMH). US was not sensitive in detecting either small cerebellar or extra-axial hemorrhage. CONCLUSION HUS was highly sensitive and specific in the evaluation of grade III GMH, whereas SWI was superior to HUS in detecting small intra-axial or extra-axial hemorrhage, and had no impact on short-term management. Given the low cost, lack of radiation and advantages of bedside evaluation, HUS should continue to be the first line of imaging for brain injury in the evaluation of premature neonates with suspected intracranial hemorrhage. However, the usefulness of SWI for predicting long-term neurological outcomes has yet to be determined.

Cerebral fat embolism syndrome in sickle cell anaemia/β-thalassemia: Importance of susceptibility-weighted MRI.

Fat embolism syndrome is a rare, but potentially lethal complication of sickle cell disease, with mortality ranging from 5e15%.1e6 Most commonly, fat embolism syndrome presents after trauma, typically after long bone fractures, but it can also occur in non-traumatic disorders including the postoperative setting, diabetes, neoplea, blood transfusions, or cardiopulmonary bypass.3,7,8 Fat embolism syndrome has been recognized as a complication of acute chest syndrome in sickle cell disease.9 After a 12e48 h symptom-free period, patients usually present with progressive respiratory distress, cerebral involvement (seizures, decreased level of consciousness, and focal neurological deficits), and skin and mucosal petechiae. Secondary diagnostic signs include fever, tachycardia, retinal changes, jaundice, and renal disease.10 Cerebral fat embolism syndrome can be seen in up to 86% of cases of fat embolism, resulting in embolic brain micro-infarcts, vasogenic oedema, and petechial haemorrhages.2 Many cases of cerebral fat embolism syndrome in sickle cell patients are not diagnosed until autopsy, highlighting the importance of recognizing this clinical entity on imaging studies.4,11e13 When recognized and treated appropriately, fat embolism syndrome in sickle cell disease is curable.9 Only a few case reports of fat embolism syndrome in sickle cell/b-thalassemia patients are in the literature,1,2,4,6,14 and there are even fewer case reports that included haem-sensitive sequences [T2 gradient echo and susceptibility weighted imaging (SWI)], but to the authors’ knowledge none of these reports included SWI.15,16