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.

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 PARTICIPANTSAn 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 wholebrain, 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 MEASURESPhysical 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,; 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 RELEVANCEThis study provides in vivo evidence that CLs are associated with cognitive and ...

Objective. Myelitis causes pain, weakness, and sphincteric deficits, and is 1,000-fold more prevalent in patients with systemic lupus erythematosus (SLE) than in the general population. For the last century, descriptions of SLE myelitis have been primarily limited to case reports. In contrast, larger-scale cohort studies have revealed that myelitis occurring in the idiopathic demyelinating diseases (i.e., multiple sclerosis versus neuromyelitis optica) represents distinct syndromes. This study was undertaken to determine whether SLE myelitis similarly encapsulates distinct syndromes.Methods. We analyzed a cohort of 22 patients with SLE and myelitis. Patients were assessed for neurologic variables related to myelitis and for clinical and serologic features of SLE. Magnetic resonance images of the spine, cerebrospinal fluid profiles, and autoantibody profiles were obtained.Results. Eleven patients presented with signs of gray matter dysfunction (i.e., flaccidity and hyporeflexia), whereas 11 patients presented with signs of white matter dysfunction (i.e., spasticity and hyperreflexia). Patients with gray matter dysfunction were more likely to have irreversible paraplegia (P < 0.01), despite presenting with a monophasic versus polyphasic course (P ‫؍‬ 0.01), higher levels of SLE activity (mean SLE Disease Activity Index 9.8 versus 2.0; P ‫؍‬ 0.01), and a cerebrospinal fluid profile indistinguishable from bacterial meningitis. Prior to irreversible paraplegia, these patients presented with prodromes of fever and urinary retention, but were misdiagnosed by physicians of different specialties as having urinary tract infections. Patients with white matter dysfunction were more likely to meet criteria for neuromyelitis optica (P ‫؍‬ 0.04) and were also more likely to have antiphospholipid antibodies (lupus anticoagulant) (P ‫؍‬ 0.01). Conclusion. Our findings indicate that SLE myelitis encapsulates 2 distinct and previously unrecognized syndromes that can be distinguished clinically by gray matter versus white matter findings. Recognition of fever and urinary retention as prodromes of irreversible paraplegia may allow earlier diagnosis and treatment in SLE patients presenting with gray matter findings.Myelitis is a devastating inflammatory syndrome of the spinal cord, causing weakness, numbness, and sphincteric deficits. Myelitis is estimated to affect 1-2% of patients with systemic lupus erythematosus (SLE) (1), more than 1,000 times greater than the prevalence of idiopathic myelitis in the general population (2). Despite this disproportionate morbidity affecting SLE patients, the last century has witnessed mostly isolated case reports of myelitis in SLE patients.SLE myelitis is traditionally regarded as a single diagnostic entity (3-5). However, subsuming all cases of myelitis in SLE patients under a unifying diagnostic rubric may be incorrect. Forms of SLE myelitis may have distinct clinical patterns, relationships to SLE activity, cerebrospinal fluid (CSF) profiles, and mechanisms of action. Such heterogeneity is di...