Karl-Olof Lövblad

The ischemic penumbra Operationally defined by diffusion and perfusion MRI

BACKGROUND Identifying tissue at risk for infarction is important in deciding which patients would benefit most from potentially harmful therapies and provides a way to evaluate newer therapies with regard to the amount of ischemic tissue salvaged. OBJECTIVE To operationally define and characterize cerebral tissue at risk for stroke progression. METHODS We retrospectively selected 25 patients with an acute onset of a hemispheric stroke from our database who had undergone a combination of two diffusion-weighted MRI studies and a perfusion-weighted MRI study. We applied a logistic regression model using maps of the relative mean transit time and relative cerebral blood flow (rCBF) as well as three different maps of the relative cerebral blood volume (rCBV) to predict an operationally defined penumbra (region of mismatch between the diffusion lesion on day 1 and its extension 24 to 72 hours later). RESULTS Maps of the rCBF and initial rCBV were significant predictors for identifying penumbral tissue. Our operationally defined penumbral region was characterized by a reduction in the initial rCBV (47% of contralateral control region [CCR]), an increase (163% of CCR) in the total rCBV, and a reduction (37% of CCR) in the rCBF, whereas the operationally defined ischemic core showed a more severe reduction in the rCBF (12% of CCR) and in the initial rCBV (19% of CCR). CONCLUSION These MR indexes may allow the identification and quantification of viable but ischemically threatened cerebral tissue amenable to therapeutic interventions in the hyperacute care of stroke patients.

Brain functional magnetic resonance imaging of rectal pain and activation of endogenous inhibitory mechanisms in irritable bowel syndrome patient subgroups and healthy controls

Background and aims: Many patients with irritable bowel syndrome (IBS) show intestinal hypersensitivity to distension and sensitisation after repeated intestinal distensions. Abnormalities in endogenous pain inhibitory mechanisms, such as diffuse noxious inhibitory controls (DNIC), may be implicated and were investigated during brain functional magnetic resonance imaging (fMRI). Patients and methods: fMRI was performed in 10 female patients with IBS (five constipated (IBS-C) and five with diarrhoea (IBS-D)) and 10 female healthy controls during rectal balloon distension alone or during activation of DNIC by painful heterotopic stimulation of the foot with ice water. Rectal pain was scored with and without heterotopic stimulation (0 = none, 10 = maximal). Results: Heterotopic stimulation decreased median rectal pain scores significantly in healthy controls (−1.5 (interquartile range −2 to −1); p = 0.001) but not in IBS-C (−0.7 (−1 to 0.5)), IBS-D (−0.5 (−1.5 to 0.5)), or in all IBS patients (0 (−1.5 to 1.3)). Brain activation changes during heterotopic stimulation differed highly significantly between IBS-C, IBS-D, and controls. The main centres affected were the amygdala, anterior cingulate cortex, hippocampus, insula, periaqueductal gray, and prefrontal cortex, which form part of the matrix controlling emotional, autonomic, and descending modulatory responses to pain. Conclusions: IBS-C and IBS-D appear to have differing abnormal endogenous pain inhibitory mechanisms, involving DNIC and other supraspinal modulatory pathways.

Neuroanatomy of hemispatial neglect and its functional components: a study using voxel-based lesion-symptom mapping

Spatial neglect is a perplexing neuropsychological syndrome, in which patients fail to detect (and/or respond to) stimuli located contralaterally to their (most often right) hemispheric lesion. Neglect is characterized by a wide heterogeneity, and a role for multiple components has been suggested, but the exact nature of the critical components remains unclear. Moreover, many different lesion sites have been reported, leading to enduring controversies about the relative contribution of different cortical and/or subcortical brain regions. Here we report a systematic anatomo-functional study of 80 patients with a focal right hemisphere stroke, who were examined by a series of neuropsychological tests assessing different clinical manifestations of neglect. We first performed a statistical factorial analysis of their behavioural performance across all tests, in order to break down neglect symptoms into coherent profiles of co-varying deficits. We then examined the neural correlates of these distinct neglect profiles using a statistical voxel-based lesion-symptom mapping method that correlated the anatomical extent of brain damage with the relative severity of deficits along the different profiles in each patient. Our factorial analysis revealed three main factors explaining 82% of the total variance across all neglect tests, which suggested distinct components related to perceptive/visuo-spatial, exploratory/visuo-motor, and allocentric/object-centred aspects of spatial neglect. Our anatomical voxel-based lesion-symptom mapping analysis pointed to specific neural correlates for each of these components, including the right inferior parietal lobule for the perceptive/visuo-spatial component, the right dorsolateral prefrontal cortex for the exploratory/visuo-motor component, and deep temporal lobe regions for the allocentric/object-centred component. By contrast, standard anatomical overlap analysis indicated that subcortical damage to paraventricular white matter tracts was associated with severe neglect encompassing several tests. Taken together, our results provide new support to the view that the clinical manifestations of hemispatial neglect might reflect a combination of distinct components affecting different domains of spatial cognition, and that intra-hemispheric disconnection due to white matter lesions might produce severe neglect by impacting on more than one functional domain.

Transvenous embolization of a ruptured deep cerebral arteriovenous malformation. A technical note.

Ruptured cerebral arteriovenous malformations (AVMs) usually require treatment to avoid re-bleeding. Depending on the angioarchitecture and center strategy, the treatment can be surgical, endovascular, radiosurgical or combined methods. The classic endovascular approach is transarterial, but sometimes it is not always applicable. The transvenous approach has been described as an alternative for the endovascular treatment of small AVMs when arterial access or another therapeutic method is not possible. This approach can be considered when the nidus is small and if there is a single draining vein. We present a technical note on a transvenous approach for the treatment of a ruptured AVM in a young patient.

Multiple acute stroke syndrome: Marker of embolic disease?

Objective: To determine the frequency and etiologic significance of multiple acute ischemic lesions in stroke. Background: Although patients may have more than one stroke during the course of their lives, acute ischemic stroke is usually thought of as a single event. Using diffusion-weighted imaging (DWI), an MRI technique that detects ischemic injury within minutes after onset, we have often observed multiple acute ischemic lesions. Methods: The MRI scans of 59 consecutively studied patients were reviewed to determine the frequency and etiologic significance of multiple acute ischemic lesions on DWI. Results: Multiple acute ischemic lesions were present in 10 (17%) of 59 patients. The lesions usually occurred within one major circulation (anterior or posterior), but in two patients (3%), lesions occurred in both cerebral hemispheres or in the anterior and the posterior circulations. The lesions often were small and resulted from presumed multiple emboli or the break-up of an embolus. Two patients had internal carotid artery occlusive disease and four had a cardiac or aortic source. In the other four patients the source was not determined. Lesions larger than 1 cm in diameter progressed to infarction, but some smaller lesions were not seen on follow-up T2-weighted imaging. Conclusions: Multiple acute stroke lesions on DWI are common and could be caused by multiple emboli or the breakup of an embolus. In some cases it might become possible to make early inferences concerning the stroke mechanism that could be of use for immediately directing the clinical work-up and treatment of the patient.

Retardation of myelination due to dietary vitamin B12 deficiency: cranial MRI findings.

Vitamin B12 deficiency is known to be associated with signs of demyelination, usually in the spinal cord. Lack of vitamin B12 in the maternal diet during pregnancy has been shown to cause severe retardation of myelination in the nervous system. We report the case of a 14 1/2-month-old child of strictly vegetarian parents who presented with severe psychomotor retardation. This severely hypotonic child had anemia due to insufficient maternal intake of vitamin B12 with associated megaloblastic anemia. MRI of the brain revealed severe brain atrophy with signs of retarded myelination, the frontal and temporal lobes being most severely affected. It was concluded that this myelination retardation was due to insufficient intake of vitamin B12 and vitamin B12 therapy was instituted. The patient responded well with improvement of clinical and imaging abnormalities. We stress the importance of MRI in the diagnosis and follow-up of patients with suspected diseases of myelination.

Diffusion-weighted MRI for monitoring neurovascular interventions.

Abstract Carotid stenting is increasingly considered as treatment for carotid artery disease. A reliable noninvasive method is desirable for assessing the safety of the procedure. Diffusion-weighted MRI (DWI) is sensitive to early brain ischaemia which becoming widely available and might therefore serve this purpose. We prospectively studied 19 patients referred for investigation of carotid artery disease by echo-planar whole-brain DWI before and within 24 h of stenting. The images obtained at a high b value were examined by two independent blinded reviewers for new high-signal areas consistent with ischaemia. We found that 15 patients had no new changes after stenting. One patient showed enlargement of a posterior watershed lesion after the procedure, which correlated with an increase in neurological deficit. Three other patients had presumed small embolic infarcts on DWI; two were asymptomatic and one had weakness at the hand that corresponded to an embolic infarct with a lesion on DWI in the hand notch. There were no false- positive or -negative results on DWI, when compared to clinical findings. DWI is thus a new method that can demonstrate neurologically silent or asymptomatic infants. It can be used to help to assess the safety and efficacy of neurovascular intervention.

Diagnostic Accuracy of Magnetic Resonance Angiography for Internal Carotid Artery Disease : A Systematic Review and Meta-Analysis

Background and Purpose— Accurate diagnosis of the degree of internal carotid artery (ICA) stenosis is needed for decisions regarding optimal stroke prevention. Noninvasive magnetic resonance angiography (MRA) is being proposed and used as a replacement for the gold standard, intra-arterial angiography. Our purpose was to perform a systematic review and diagnostic meta-analysis to determine the sensitivity and specificity of time-of-flight (TOF) MRA and contrast-enhanced (CE) MRA for the detection of (1) high-grade (≥70% to 99%) ICA stenoses; (2) ICA occlusions; (3) moderately severe (50% to 69%) ICA stenoses; and (4) compare the overall accuracy of the 2 MRA techniques. Methods— The medical literature on MRA and the diagnosis of ICA steno-occlusive disease was reviewed through the PubMed, EMBASE, and SCOPUS databases. All publication years were included through to November 2006. Studies were eligible for inclusion if they compared the accuracy of TOF or CE MRA for the detection of ICA disease against intra-arterial angiography and reported sufficient data. Results— The overall sensitivity of TOF MRA for the detection of ≥70% to 99% ICA stenoses was 91.2% (95% CI: 88.9% to 93.1%) with a specificity of 88.3% (86.7% to 89.7%), whereas the sensitivity of CE MRA was 94.6% (92.4% to 96.4%) with a specificity of 91.9% (90.3% to 93.4%). For the detection of ICA occlusions, the sensitivity of TOF MRA was 94.5% (91.2% to 96.8%) and the specificity was 99.3% (98.9% to 99.6%), whereas the sensitivity and specificity values for CE MRA were 99.4% (96.8% to 100%) and 99.6% (99.2% to 99.9%), respectively. For moderately severe (50% to 69%) stenoses, TOF MRA had a sensitivity of only 37.9% (29.3% to 47.1%) and a specificity of 92.1% (89.6% to 94.1%); for CE MRA, the pooled sensitivity value was somewhat better at 65.9% (57.0% to 74.0%), whereas the specificity was 93.5% (91.3% to 95.3%). Conclusions— TOF MRA and CE MRA showed high accuracy for the detection of high-grade ICA stenoses and occlusions with CE MRA having the edge over TOF MRA, but had only poor (TOF MRA) to fair (CE MRA) sensitivity for the detection of moderately severe stenoses.

Diffusion-Weighted MR in Cerebral Venous Thrombosis

The diagnosis of cerebral venous thrombosis is often difficult both clinically and radiologically and until now there is no method available to predict if brain lesions, detected clinically and using conventional brain imaging methods, may lead to full recovery, as expected in vasogenic edema or ischemic infarcts and even a hematoma. New fast neuroimaging techniques such as diffusion-weighted imaging (DWI) are sensitive to different reasons of changes in local tissular water concentration thus giving further insight into the pathophysiological mechanism as well as prognosis of cerebral venous thrombosis. We report the cases of 18 consecutive patients with a diagnosis of cerebral venous thrombosis based on clinical and imaging criteria. All patients underwent magnetic resonance imaging (MRI) of the brain, which comprised isotropic diffusion-weighted MR. Diffusion-weighted MRI showed positive findings in 17/18 cases. In 7 cases the clot could be directly visualized as an area of hyperintensity in the affected vein on DWI. In 7 cases DWI showed areas of signal loss corresponding to hematomas. In 6 cases DWI showed changes in signal intensity that were more subtle. In 4 cases of superficial venous thrombosis, there were areas of decreased ADC values (0.65–0.79 × 10–3 mm2/s) whereas in 2 cases of deep venous thrombosis, increased DWI intensities could be found that corresponded to both an increase and a decrease in ADC, corresponding to a coexistence of cytotoxic and vasogenic edemas. Diffusion-weighted MRI can demonstrate directly the presence of an intravenous clot in a select number of patients. It can also demonstrate early ischemic changes, and can differentiate conventional T2-weighted MR areas of cytotoxic from vasogenic edema.

High-resolution and functional magnetic resonance imaging of the brachial plexus using an isotropic 3D T2 STIR (Short Term Inversion Recovery) SPACE sequence and diffusion tensor imaging

This technical note demonstrates the relevance of the isotropic 3D T2 turbo-spin-echo (TSE) sequence with short-term inversion recovery (STIR) and variable flip angle RF excitations (SPACE: Sampling Perfection with Application optimized Contrasts using different flip angle Evolutions) for high-resolution brachial plexus imaging. The sequence was used in 11 patients in the diagnosis of brachial plexus pathologies involving primary and secondary tumors, and in six volunteers. We show that 3D STIR imaging is not only a reliable alternative to 2D STIR imaging, but it also better evaluates the anatomy, nerve site compression and pathology of the plexus, especially to depict space-occupying tumors along its course. Finally, due to its appropriate contrast we describe how 3D-STIR can be used as a high-resolution mask to be fused with fraction of anisotropy (FA) maps calculated from diffusion tensor imaging (DTI) data of the plexus.