Transplantation of Human Neural Precursor Cells Reverses Syrinx Growth in a Rat Model of Post-Traumatic Syringomyelia.

Posttraumatic syringomyelia (PTS) is a serious condition of progressive expansion of spinal cord cysts, affecting patients with spinal cord injury years after injury. To evaluate neural cell therapy to prevent cyst expansion and potentially replace lost neurons, we developed a rat model of PTS. We combined contusive trauma with subarachnoid injections of blood, causing tethering of the spinal cord to the surrounding vertebrae, resulting in chronically expanding cysts. The cysts were usually located rostral to the injury, extracanalicular, lined by astrocytes. T2*-weighted magnetic resonance imaging (MRI) showed hyperintense fluid-filled cysts but also hypointense signals from debris and iron-laden macrophages/microglia. Two types of human neural stem/progenitor cells-fetal neural precursor cells (hNPCs) and neuroepithelial-like stem cells (hNESCs) derived from induced pluripotent stem cells-were transplanted to PTS cysts. Cells transplanted into cysts 10 weeks after injury survived at least 10 weeks, migrated into the surrounding parenchyma, but did not differentiate during this period. The cysts were partially obliterated by the cells, and cyst walls often merged with thin layers of cells in between. Cyst volume measurements with MRI showed that the volumes continued to expand in sham-transplanted rats by 102%, while the cyst expansion was effectively prevented by hNPCs and hNESCs transplantation, reducing the cyst volumes by 18.8% and 46.8%, respectively. The volume reductions far exceeded the volume of the added human cells. Thus, in an animal model closely mimicking the clinical situation, we provide proof-of-principle that transplantation of human neural stem/progenitor cells can be used as treatment for PTS.

Gastrointestinal bleeding in a patient with a continuous-flow biventricular assist device.

The association between continuous-flow left ventricular assist devices (CF-LVADs) and gastrointestinal (GI) bleeding from angiodysplasia is well recognized. However, the association between continuous-flow biventricular assist devices (CF-BIVADs) and bleeding angiodysplasia is less understood. We report a case of GI bleeding from a patient with a CF-BIVAD. The location of GI bleeding was identified by nuclear red blood cell bleeding scan. The vascular malformation leading to the bleed was identified and localized on angiography and then by pathology. The intensity of bleeding, reflected by number of units of packed red blood cells needed for normalization of hemoglobin, as well as the time to onset of bleeding after transplantation, are similar to that seen in the literature for CF-LVADs and pulsatile BIVADs. While angiography only detected a dilated late draining vein, pathology demonstrated the presence of both arterial and venous dilation in the submucosa, vascular abnormalities characteristic of a late arteriovenous malformation.

Assessing reperfusion with whole-brain arterial spin labeling: a noninvasive alternative to gadolinium.

BACKGROUND AND PURPOSE: Arterial spin labeling (ASL) is a perfusion imaging technique that does not require gadolinium. The study aimed to assess the reliability of ASL for evaluating reperfusion in acute ischemic stroke in comparison with dynamic susceptibility contrast (DSC) imaging. METHODS: The study included 24 patients with acute ischemic stroke on admission and 24-hour follow-up ASL and DSC scans. Two readers rated images for interpretability and evidence of reperfusion. Cohen unweighted κ was used to assess (1) inter-rater reliability between readers for determining interpretability and the presence of reperfusion, (2) agreement between ASL and DSC for determining reperfusion for individual raters, and (3) agreement between ASL and DSC for determining reperfusion after consensus. RESULTS: Inter-rater reliability for both ASL and DSC was moderate to good (κ of 0.67 versus 0.55, respectively). Reader 1 rated 16 patients as having interpretable ASL and DSC when compared with 15 patients for reader 2. The κ between ASL and DSC for determining reperfusion was 0.50 for reader 1 and 0.595 for reader 2. After consensus, 18 ASL and 17 DSC image sets were rated interpretable for reperfusion and 13 had both interpretable ASL and DSC scans, yielding a κ for assessment of reperfusion of 0.8. CONCLUSIONS: Inter-rater reliability of ASL and DSC was moderate to good. Agreement between ASL and DSC for determining reperfusion was moderate for each individual rater and increased substantially after consensus. ASL is a noninvasive and practical alternative to DSC for reperfusion assessments in patients with confirmed acute ischemic stroke.

Whole-brain arterial spin labeling perfusion MRI in patients with acute stroke.

BACKGROUND AND PURPOSE: Perfusion MRI can be used to identify patients with acute ischemic stroke who may benefit from reperfusion therapies. The risk of nephrogenic systemic fibrosis, however, limits the use of contrast agents. Our objective was to evaluate the ability of arterial spin labeling (ASL), an alternative noninvasive perfusion technique, to detect perfusion deficits compared with dynamic susceptibility contrast (DSC) perfusion imaging. METHODS: Consecutive patients referred for emergency assessment of suspected acute stroke within a 7-month period were imaged with both ASL and DSC perfusion MRI. Images were interpreted in a random order by 2 experts blinded to clinical information for image quality, presence of perfusion deficits, and diffusion-perfusion mismatches. RESULTS: One hundred fifty-six patients were scanned with a median time of 5.6 hours (range, 3.0-17.7 hours) from last seen normal. Stroke diagnosis was clinically confirmed in 78 patients. ASL and DSC imaging were available in 64 of these patients. A perfusion deficit was detected with DSC in 39 of these patients; ASL detected 32 of these index perfusion deficits, missing 7 lesions. The median volume of the perfusion deficits as determined with DSC was smaller in patients who were evaluated as normal with ASL than in those with a deficit (median [interquartile range], 56 [10-116] versus 114 [41-225] mL; P=0.01). CONCLUSIONS: ASL can depict large perfusion deficits and perfusion-diffusion mismatches in correspondence with DSC. Our findings show that a fast 2½-minute ASL perfusion scan may be adequate for screening patients with acute stroke with contraindications to gadolinium-based contrast agents.

Pseudocontinuous arterial spin labeling quantifies relative cerebral blood flow in acute stroke.

BACKGROUND AND PURPOSE: The aim of this study was to test whether arterial spin labeling (ASL) can detect significant differences in relative cerebral blood flow (rCBF) in the core, mismatch, and reverse-mismatch regions, and whether rCBF values measured by ASL in those areas differ from values obtained using dynamic susceptibility contrast (DSC) MRI. METHODS: Acute stroke patients were imaged with diffusion-weighted imaging (DWI) and perfusion-weighted imaging (ASL and DSC) MRI. An expert reader segmented the ischemic lesion on DWI and the DSC time-to-peak (TTP) maps. Three regions were defined: core (DWI+, TTP+), mismatch (DWI-, TTP+), and reverse-mismatch (DWI+, TTP-). For both ASL and DSC, rCBF maps were created with commercially available software, and the ratio was calculated as the mean signal intensity measured on the side of the lesion to that of the homologous region in the contralateral hemisphere. Values obtained from core, mismatch, and reverse-mismatch were used for paired comparison. RESULTS: Twenty-eight patients were included in the study. The mean age was 65.6 (16.9) years, with a median baseline National Institutes of Health Stroke Scale score of 10 (interquartile range, 4-17). Median time from last known normal to MRI was 5.7 hours (interquartile range, 2.9-22.6). Mean rCBF ratios were significantly higher in the mismatch 0.53 (0.23) versus the core 0.39 (0.33) and reverse-mismatch 0.68 (0.49) versus the core 0.38 (0.35). Differences in rCBF measured with DSC and ASL were not significant. CONCLUSIONS: ASL allows for the measurement of rCBF in the core and mismatch regions. Values in the mismatch were significantly higher than in the core, suggesting there is potential salvageable tissue.