Sverre Rosenbaum

Cerebral Perfusion and Cerebrovascular Reactivity Are Reduced in White Matter Hyperintensities

Background and Purpose— There is growing evidence that white matter hyperintensities (WMH) should not be considered as benign age-dependent changes on MR images but indicate pathological changes with clinical consequences. Previous studies comparing subjects with WMH to normal controls have reported global reductions in cerebral blood flow (CBF) and cerebral vascular reactivity. In this study, we examined localized hemodynamic status to compare WMH to normal appearing white matter (NAWM). Methods— A group of 21 normal 85-year-old subjects were studied using dynamic contrast-enhanced MRI together with administration of acetazolamide. From a combination of anatomic images with different signal weighting, regions of interest were generated corresponding to gray and white matter and WMH. Localized measurements of CBF and cerebral blood volume (CBV) and mean transit time were obtained directly within WMH and NAWM. Results— When comparing WMH to NAWM, measurements showed significantly lower CBF (P =0.004) and longer mean transit time (P < 0.001) in WMH but no significant difference in CBV (P =0.846). The increases in CBF and CBV induced by acetazolamide were significantly smaller in WMH than in NAWM (P =0.026, P <0.001). Conclusion— These results show that a change in the hemodynamic status is present within the WMH, making these areas more likely to be exposed to transient ischemia inducing myelin rarefaction. In the future, MRI may be used to examine the effect of therapeutic strategies designed to prevent or normalize vascular changes.

Quantification of the effect of water exchange in dynamic contrast MRI perfusion measurements in the brain and heart.

Measurement of myocardial and brain perfusion when using exogenous contrast agents (CAs) such as gadolinium‐DTPA (Gd‐DTPA) and MRI is affected by the diffusion of water between compartments. This water exchange may have an impact on signal enhancement, or, equivalently, on the longitudinal relaxation rate, and could therefore cause a systematic error in the calculation of perfusion (F) or the perfusion‐related parameter, the unidirectional influx constant over the capillary membranes (Ki). The aim of this study was to quantify the effect of water exchange on estimated perfusion (F or Ki) by using a realistic simulation. These results were verified by in vivo studies of the heart and brain in humans. The conclusion is that water exchange between the vascular and extravascular extracellular space has no effect on Ki estimation in the myocardium when a normal dose of Gd‐DTPA is used. Water exchange can have a significant effect on perfusion estimation (F) in the brain when using Gd‐DTPA, where it acts as an intravascular contrast agent. Magn Reson Med 46:272–281, 2001.

Paroxysmal atrial fibrillation occurs often in cryptogenic ischaemic stroke. Final results from the SURPRISE study

Atrial fibrillation (AF) increases the risk of stroke fourfold and is associated with a poor clinical outcome. Despite work‐up in compliance with guidelines, up to one‐third of patients have cryptogenic stroke (CS). The prevalence of asymptomatic paroxysmal atrial fibrillation (PAF) in CS remains unknown. The SURPRISE project aimed at determining this rate using long‐term cardiac monitoring.

Corticospinal tract degeneration and possible pathogenesis in ALS evaluated by MR diffusion tensor imaging

BACKGROUND: MR diffusion tensor imaging (DTI) appears to be a powerful method to investigate the neuronal and axonal fibre distribution in the human brain. Changes in diffusion characteristics of water molecules in the white matter can be estimated as the apparent diffusion coefficient (ADC) and the fractional anisotropy index (FA). OBJECTIVES: To characterize DTI changes at three different levels in the corticospinal tract (CST) (corona radiata, internal capsule and pons) in order to elucidate if pathogenesis of ALS is due to an anterograde or retrograde axonal degeneration. METHODS: We studied eight ALS patients with clinical signs of upper motor neuron involvement. The patients were compared with 11 healthy age‐matched controls. RESULTS: ADC was significantly increased in the CST in ALS patients at the level of the internal capsule and also increased in the pons, but without statistical significance. ADC was unchanged at the level of the corona radiata. FA was significantly reduced at the lowest level (pons), only tended to be reduced in the internal capsule, but was also unchanged in the corona radiata. CONCLUSIONS: Segmentation of the CST into three regions supports the hypothesis of a ‘dying back’ mechanism in ALS and suggests that ADC is a more sensitive measure than FA to detect pathological changes in ALS.

N-Acetylaspartate Distribution in Rat Brain Striatum During Acute Brain Ischemia

Brain N-acetylaspartate (NAA) can be quantified by in vivo proton magnetic resonance spectroscopy (1H-MRS) and is used in clinical settings as a marker of neuronal density. It is, however, uncertain whether the change in brain NAA content in acute stroke is reliably measured by 1H-MRS and how NAA is distributed within the ischemic area. Rats were exposed to middle cerebral artery occlusion. Preischemic values of [NAA] in striatum were 11 mmol/L by 1H-MRS and 8 mmol/kg by HPLC. The methods showed a comparable reduction during the 8 hours of ischemia. The interstitial level of [NAA] ([NAA]e) was determined by microdialysis using [3H]NAA to assess in vivo recovery. After induction of ischemia, [NAA]e increased linearly from 70 µmol/L to a peak level of 2 mmol/L after 2 to 3 hours before declining to 0.7 mmol/L at 7 hours. For comparison, [NAA]e was measured in striatum during global ischemia, revealing that [NAA]e increased linearly to 4 mmol/L after 3 hours and this level was maintained for the next 4 h. From the change in in vivo recovery of the interstitial space volume marker [14C]mannitol, the relative amount of NAA distributed in the interstitial space was calculated to be 0.2% of the total brain NAA during normal conditions and only 2 to 6% during ischemia. It was concluded that the majority of brain NAA is intracellularly located during ischemia despite large increases of interstitial [NAA]. Thus, MR quantification of NAA during acute ischemia reflects primarily changes in intracellular levels of NAA.

Cerebral hemodynamic changes measured by gradient-echo or spin-echo bolus tracking and its correlation to changes in ICA blood flow measured by phase-mapping MRI

Changes in cerebral blood flow (CBF) induced by Acetazolamide (ACZ) were measured using dynamic susceptibility contrast MRI (DSC‐MRI) with both spin echo (SE) EPI and gradient echo (GE) EPI, and related to changes in internal carotid artery (ICA) flow measured by phase‐mapping. Also examined was the effect of repeated bolus injections. CBF, cerebral blood volume (CBV), and mean transit time (MTT) were calculated by singular value decomposition (SVD) and by deconvolution using an exponential function as kernel. The results showed no dependency on calculation method. GE‐EPI measured a significant increase in CBF and CBV in response to ACZ, while SE‐EPI measured a significant increase in CBV and MTT. CBV and MTT change measured by SE‐EPI was sensitive to previous bolus injections. There was a significant linear relation between change in CBF measured by GE‐EPI and change in ICA flow. In conclusion, GE‐EPI under the present condition was superior to SE‐EPI in monitoring cerebral vascular changes.J. Magn. Reson. Imaging 2001;14:391–400.

Time Course of Early Postadmission Hematoma Expansion in Spontaneous Intracerebral Hemorrhage

Background and Purpose— Early hematoma expansion (EHE) in patients with intracerebral hematoma is a promising treatment target. To date, the time course of EHE has remained poorly described. We prospectively investigated the time course of EHE. Methods— We included consecutive patients presenting spontaneous intracerebral hematoma within 4.5 hours. On admission, patients underwent noncontrast computed tomography (CT) and CT angiography. Serial hematoma volume estimations by transcranial B-mode ultrasound were effected through the contralateral transtemporal bone window by obtaining sagittal, transversal, and coronal diameter and calculating the ABC/2-formula. National Institute of Health Stroke Scale and transcranial B-mode ultrasound were performed consecutively every 30 minutes during the first 6 hours and from 6 to 12 hours every 2 hours. Follow-up CT and ultrasound were performed after ≈24 hours. Results— Twenty-five patients with intracerebral hematoma were included; mean (SD) time from onset to CT was 108.6 (45.7) minutes. Ten (40%) patients had EHE. In patients with a final clinically significant hematoma expansion >12.5 mL, all EHE occurred within 6 hours after admission scan. EHE in spot sign positive patients continued during the first 5 hours after CT angiography. In spot sign–negative patients, no significant EHE was observed (Friedman test, P=0.476). Neurological deterioration occurred in 5 (20%) patients and was well temporally correlated with EHE. Transcranial B-mode ultrasound demonstrated good volume estimation compared with the follow-up CT with a maximum absolute volume deviation within 7 mL and minimal systematic error (mean deviation, 1.3 [confidence interval, −0.1 to 2.6] mL). Conclusions— EHE was reliably reflected by transcranial B-mode ultrasound and mainly occurred within the first 7 to 8 hours after symptom onset. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT01472224.

Prediction and observation of post-admission hematoma expansion in patients with intracerebral hemorrhage.

Post-admission hematoma expansion in patients with intracerebral hemorrhage (ICH) comprises a simultaneous major clinical problem and a possible target for medical intervention. In any case, the ability to predict and observe hematoma expansion is of great clinical importance. We review radiological concepts in predicting and observing post-admission hematoma expansion. Hematoma expansion can be observed within the first 24 h after symptom onset, but predominantly occurs in the early hours. Thus capturing markers of on-going bleeding on imaging techniques could predict hematoma expansion. The spot sign observed on computed tomography angiography is believed to represent on-going bleeding and is to date the most well investigated and reliable radiological predictor of hematoma expansion as well as functional outcome and mortality. On non-contrast CT, the presence of foci of hypoattenuation within the hematoma along with the hematoma-size is reported to be predictive of hematoma expansion and outcome. Because patients tend to arrive earlier to the hospital, a larger fraction of acute ICH-patients must be expected to undergo hematoma expansion. This renders observation and radiological follow-up investigations increasingly relevant. Transcranial duplex sonography has in recent years proven to be able to estimate hematoma volume with good precision and could be a valuable tool in bedside serial observation of acute ICH-patients. Future studies will elucidate, if better prediction and observation of post-admission hematoma expansion can help select patients, who will benefit from hemostatic treatment.

Inducible limb-shaking transitory ischemic attacks: a video-documented case report and review of the literature

BackgroundLimb-shaking transient ischemic attack (TIA) is a well-recognized, but rare observation in contralateral carotid steno-occlusive disease. Consequently, most clinicians have not had the chance to witness an attack.Case presentationWe present the story of a 64-year old gentleman with exercise-induced weakness associated with tremor in his right arm. His left internal carotid artery was occluded at the bifurcation. Administration of statin and antiplatelet did not relieve his symptoms, and his stereotypic, exercise-induced “limb-shaking” episodes persisted. He underwent successful extracranial to intracranial (EC-IC) bypass, which stopped his symptoms. The patient, however, returned to our department and reported that he was able to recreate his original symptoms by compressing the bypass graft manually.ConclusionTo our knowledge, this is the first case with video documentation of the clinical appearance of a limb-shaking TIA. We hope this case report will increase the physicians’ understanding of the clinical nature of limb-shaking TIAs.

Comparison of 3- and 20-Gradient Direction Diffusion-Weighted Imaging in a Clinical Subacute Cohort of Patients with Transient Ischemic Attack: Application of Standard Vendor Protocols for Lesion Detection and Final Infarct Size Projection

Objective Diffusion tensor imaging may aid brain ischemia assessment but is more time consuming than conventional diffusion-weighted imaging (DWI). We compared 3-gradient direction DWI (3DWI) and 20-gradient direction DWI (20DWI) standard vendor protocols in a hospital-based prospective cohort of patients with transient ischemic attack (TIA) for lesion detection, lesion brightness, predictability of persisting infarction, and final infarct size. Methods We performed 3T-magnetic resonance imaging including diffusion and T2-fluid attenuated inversion recovery (FLAIR) within 72 h and 8 weeks after ictus. Qualitative lesion brightness was assessed by visual inspection. We measured lesion area and brightness with manual regions of interest and compared with homologous normal tissue. Results 117 patients with clinical TIA showed 78 DWI lesions. 2 lesions showed only on 3DWI. No lesions were uniquely 20DWI positive. 3DWI was visually brightest for 34 lesions. 12 lesions were brightest on 20DWI. The median 3DWI lesion area was larger for lesions equally bright, or brightest on 20DWI [median (IQR) 39 (18–95) versus 18 (10–34) mm2, P = 0.007]. 3DWI showed highest measured relative lesion signal intensity [median (IQR) 0.77 (0.48–1.17) versus 0.58 (0.34–0.81), P = 0.0006]. 3DWI relative lesion signal intensity was not correlated to absolute signal intensity, but 20DWI performed less well for low-contrast lesions. 3DWI lesion size was an independent predictor of persistent infarction. 3-gradient direction apparent diffusion coefficient areas were closest to 8-week FLAIR infarct size. Conclusion 3DWI detected more lesions and had higher relative lesion SI than 20DWI. 20DWI appeared blurred and did not add information. Clinical Trial Registration http://www.clinicaltrials.gov. Unique Identifier NCT01531946.