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Selection of the optimum b factor for diffusion-weighted magnetic resonance imaging assessment of ischemic stroke.

The purpose of this study was to determine the diffusion sensitivity factor b that optimizes the contrast-to-noise ratio (CNR) for both diffusion-weighted signal intensity and the apparent diffusion coefficient (ADCNR) when evaluating ischemic stroke by diffusion-weighted MRI. The relative contrast, noise levels, CNR, and ADCNR were calculated for typical ADC values in human brain, 780 microm(2)/s in adults and 1200 microm(2)/s in neonates in normal tissue, 20-40% less in acute and subacute stroke, and 50% more in chronic stroke. The optimum b factor depends strongly on the ADC, whether TE is fixed or varies with the b factor, whether CNR or ADCNR is measured, and anisotropy. The optimum b factor in adults is 1000 s/mm(2) in acute and chronic stroke, and 1200 s/mm(2) in subacute stroke. The optimum values are about 200 s/mm(2) lower in neonates than in adults. The CNR and ADCNR are within 10% of the optimum over at least a 2-fold range of b factors, from 68-136% of the optimum b factor. If a single b factor is to be used for all situations, a diffusion b factor of 1000 s/mm(2) is recommended.

Acute Disease↗

Sporadic Creutzfeldt-Jakob disease: a comparison of pathological findings and diffusion weighted imaging.

To investigate a possible relationship between the severity of pathological and radiological lesions in diffusion-weighted MRI (DWI) we compared DWI findings from 6 sequential brain MRI scans with pathological features of numerous tissue blocks of different cortical and subcortical regions in a case of autopsy-proven sporadic CJD. Whereas DWI and pathological examination revealed multifocal, cortical and deep hyperintensities at corresponding localizations, no correlation between the degree of severity of radiologically visible and pathological damage was found. The characteristic focal involvement and extension of lesions of the cortex and the basal ganglia bilaterally shown by DWI may be an argument for the spreading of the disease per contiguitatem.

Cell Death↗

Is the ABCD score useful for risk stratification of patients with acute transient ischemic attack?

BACKGROUND AND PURPOSE: A 6-point scoring system (ABCD) was described recently for stratifying risk after transient ischemic attack (TIA). This score incorporates age (A), blood pressure (B), clinical features (C), and duration (D) of TIA. A score <4 reportedly indicates minimal short-term stroke risk. We evaluated this scoring system in an independent population. METHODS: This was a prospective study of TIA patients (diagnosed by a neurologist using the classic <24-hour definition) hospitalized <48 hours from symptom onset. The primary outcome assessment consisted of dichotomization of patients into 2 groups. The high-risk group included patients with stroke or death within 90 days, > or =50% stenosis in a relevant artery, or a cardioembolic source warranting anticoagulation. All others were classified as low risk. Findings on diffusion-weighted MRI (DWI) were also evaluated when performed and patients classified as DWI+ or DWI-. RESULTS: Over 3 years, 117 patients were enrolled. Median time from symptom onset to enrollment was 25.2 hours (interquartile range 19.8 to 30.2). Overall, 26 patients (22%) were classified as high risk, including 2 strokes, 2 deaths, 15 with > or =50% stenosis, and 10 with cardioembolic source. The frequency of high-risk patients increased with ABCD score (0 to 1 13%; 2 8%; 3 17%; 4 27%; 5 26%; 6 30%; P for trend=0.11). ABCD scores in the 2 patients with stroke were 3 and 6. Of those who underwent MRI, 15 of 61 (25%) were DWI+, but this correlated poorly with ABCD score (0 to 1 17%; 2 10%; 3 36%; 4 24%; 5 13%; 6 60%; P for trend=0.24). CONCLUSIONS: Although the ABCD score has some predictive value, patients with a score <4 still have a substantial probability of having a high-risk cause of cerebral ischemia or radiographic evidence of acute infarction despite transient symptoms.

Age Factors↗

Effect of intravenous thrombolysis on MRI parameters and functional outcome in acute stroke <6 hours.

BACKGROUND AND PURPOSE: The goals of this study were to examine MRI baseline characteristics of patients with acute ischemic stroke (AIS) and to study the influence of intravenous tissue plasminogen activator (tPA) on MR parameters and functional outcome using a multicenter approach. METHODS: In this open-label, nonrandomized study of AIS patients with suspected anterior circulation stroke, subjects received a multiparametric stroke MRI protocol (diffusion- and perfusion-weighted imaging and MR angiography) within 6 hours after symptom onset and on follow-up. Patients were treated either with tPA (thrombolysis group) or conservatively (no thrombolysis group). Functional outcome was assessed on day 90 (modified Rankin Score; mRS). RESULTS: We enrolled 139 AIS patients (no thrombolysis group, n=63; thrombolysis group, n=76). Patients treated with tPA were more severely affected (National Institutes of Health Stroke Scale score, 10 versus 13; P=0.002). Recanalization rates were higher in the thrombolysis group (Thrombolysis in Myocardial Infarction criteria 1 through 3 on day 1; 66.2% versus 32.7%; P<0.001). Proximal vessel occlusions resulted in larger infarct volumes and worse outcome (P=0.02). Thrombolysis was associated with a better outcome regardless of the time point of tPA treatment (< or =3 hours or 3 to 6 hours) (univariate analysis: mRS < or =2, P=0.017; mRS < or =1, P=0.023). Age (P=0.003), thrombolytic therapy at 0 to 6 hours (P=0.01), recanalization (P=0.016), lesion volume on day 7 (P=0.001), and initial National Institutes of Health Stroke Scale score (P=0.001) affected functional outcome (mRS on day 90) positively (multivariate analysis). The time point of tPA therapy affected the recanalization rate (P=0.024) but not final infarct volume. CONCLUSIONS: In this pilot study, tPA therapy had a beneficial effect on vessel recanalization and functional outcome. Multiparametric MRI delineates tissue at risk of infarction in AIS patients, which may be helpful for the selection of patients for tPA therapy. tPA therapy appeared safe and effective beyond a 3-hour time window. This study delivers the rationale for a randomized, MR-based tPA trial.

Acute Disease↗

Confidence mapping in diffusion tensor magnetic resonance imaging tractography using a bootstrap approach.

The bootstrap technique is an extremely powerful nonparametric statistical procedure for determining the uncertainty in a given statistic. However, its use in diffusion tensor MRI tractography remains virtually unexplored. This work shows how the bootstrap can be used to assign confidence to results obtained with deterministic tracking algorithms. By invoking the concept of a "tract-propagator," it also underlines the important effect of local fiber architecture or architectural milieu on tracking reproducibility. Finally, the practical advantages and limitations of the technique are discussed. Not only does the bootstrap allow any deterministic tractography algorithm to be used in a probabilistic fashion, but also its model-free inclusion of all sources of variability (including those that cannot be modeled) means that it provides the most realistic approach to probabilistic tractography.

Algorithms↗

Silent cerebral ischaemia: hidden fingerprints of invasive medical procedures.

Cardiovascular and cerebrovascular disorders are the main cause of death and permanent disability worldwide. Improved diagnostic and therapeutic options for these diseases have led to increasing numbers of invasive procedures such as angiography, stent placement, and operations exceeding 4 million each year in the USA. Although clinical examinations suggest a relatively low risk for ischaemic complications affecting the brain, new magnetic resonance techniques have led to the awareness of much higher numbers of clinically silent ischaemic brain lesions. Diffusion-weighted MRI (DWI) has shown new ischaemic lesions in a substantial number of patients undergoing cardiac or carotid-artery surgery, and coronary or cerebral-angiographic interventions. The clinical impact of these "silent" ischaemic lesions within brain areas without primary motor, sensory, or linguistic function ("non-eloquent" brain areas) is debated. There is increasing evidence, however, that cumulative burden of ischaemic brain injury causes neuropsychological deficits or aggravates vascular dementia. Thus, DWI emerges as a valuable diagnostic method for the monitoring of periprocedural ischaemic events in the brain, and could be a surrogate parameter for optimising diagnostic and therapeutic vascular procedures in the future.

Brain↗

Erythropoietin improves functional and histological outcome in neonatal stroke.

Neonatal stroke is a condition that leads to disability in later life, and as yet there is no effective treatment. Recently, erythropoietin (EPO) has been shown to be cytoprotective following brain injury and may promote neurogenesis. However, the effect of EPO on functional outcome and on morphologic changes in neonatal subventricular zone (SVZ) following experimental neonatal stroke has not been described. We used a transient focal model of neonatal stroke in P10 rat. Injury was documented by diffusion weighted MRI during occlusion. Immediately upon reperfusion, either EPO (5U/gm) or vehicle was administered intraperitoneally and animals were allowed to grow for 2 wk. Sensorimotor function was assessed using the cylinder rearing test and then brains were processed for volumetric analysis of the SVZ. Stroke induced SVZ expansion proportional to hemispheric volume loss. EPO treatment markedly preserved hemispheric volume and decreased the expansion of SVZ unilaterally. Furthermore, EPO treatment significantly improved the asymmetry of forelimb use following neonatal stroke. This functional improvement directly correlated with the amount of preserved hemispheric volume. These results suggest EPO may be a candidate in the treatment of neonatal stroke.

Animals↗

Calculation of apparent diffusion coefficients (ADCs) in brain using two-point and six-point methods.

We evaluated the relative accuracy of calculating apparent diffusion coefficients (ADCs) of intracranial tissues using a two-point versus a six-point regression technique. Echo planar diffusion-weighted MRI was performed at 1.5 T in three standard locations and in pathologic regions in 10 subjects using gradient strengths corresponding to b values of 1, 100, 200, 500, 800, and 1,000 s/mm2. Estimation of ADCs was made using two methods: a nonlinear regression model using measurements from the full set of b values (six-point technique) and linear estimation using b values of 1 and 1,000 only (two-point technique). A high correlation between the two methods was noted (R2 = 0.999), and the mean percentage difference was 0.84%. These results suggest there is little error in estimating brain ADCs using a two-point technique.

Adult↗

White matter tract alterations in fragile X syndrome: preliminary evidence from diffusion tensor imaging.

Fragile X syndrome, the most common form of hereditary mental retardation, causes disruption in the development of dendrites and synapses, the targets for axonal growth in the central nervous system. This disruption could potentially affect the development, wiring, and targeting of axons. The current study utilized diffusion tensor imaging (DTI) to investigate whether white matter tract integrity and connectivity are altered in fragile X syndrome. Ten females with a diagnosis of fragile X syndrome and ten, age matched, female control subjects underwent diffusion weighted MRI scans. A whole brain analysis of fractional anisotropy (FA) values was performed using statistical parametric mapping (SPM). A follow-up, regions-of-interest analysis also was conducted. Relative to controls, females with fragile X exhibited lower FA values in white matter in fronto-striatal pathways, as well as in parietal sensory-motor tracts. This preliminary study suggests that regionally specific alterations of white matter integrity occur in females with fragile X. Aberrant white matter connectivity in these regions is consistent with the profile of cognitive and behavioral features of fragile X syndrome, and potentially provide additional insight into the detrimental effects of suboptimal levels of FMRP in the developing brain.

Adolescent↗

Imaging of neck metastases.

Awareness of the presence of cervical node metastasis is important in treatment planning and in prognostic prediction for patients with head and neck cancer. Currently, MRI and CT are commonly used to evaluate the primary tumor and the neck status. They characterize the cervical lymph nodes dependent on morphological criteria. However, metastases may be missed in some morphologically normal nodes. Conversely, it is difficult to discriminate reactive hyperplasia from metastasis in some enlarged nodes. Doppler ultrasound with fine-needle aspiration can overcome some of these limitations, but it is dependent on the sonographer's skill level and may be impractical in some cases due to too many questionable nodes. Positron emission tomography (PET) is a functional imaging that can detect metastasis lesions by pinpointing regions of high metabolism. It is better suited for assessing metastases to lymph nodes that appear morphologically normal. The main drawback of PET is its poor anatomical resolution. Side-by-side visual correlation of PET and CT/MRI can help determine the anatomical location of abnormal PET uptake and eliminate some false-positive PET findings caused by spatial errors. Fused PET/CT is considered to be the most accurate imaging modality for detecting nodal metastases, because it simultaneously provides prompt and accurate coregistration of functional and anatomical images. However, it is expensive, less-often available, and still constrained by technical resolution limits for tiny nodal metastases. Diffusion-weighted MRI, dynamic contrast-enhanced MRI, and nanoparticle-enhanced MRI are novel imaging technologies that have been exploited to enhance the detection of metastatic nodes. The initial results have been promising; however, micrometastases can still not be detected, and the extra costs and logistical burdens associated with these techniques prevent them from gaining wider acceptance. To date, neck dissection with detailed pathological examination is the gold standard. There is always a need for further refinement of the imaging techniques that can provide accurate information that approaches this gold standard.

Head and Neck Neoplasms↗

Small centrum ovale infarcts on diffusion-weighted magnetic resonance imaging.

BACKGROUND AND PURPOSE: A small centrum ovale infarct (SCOI), caused by occlusion of the white matter medullary arteries, is often equated with a lacunar infarct. We sought to clarify the clinical characteristics of a SCOI visualized by diffusion-weighted MRI (DWI) compared with those of a small basal ganglia infarct (SBGI). METHODS: Patients with a SCOI (SCOI group; n=38) or SBGI (SBGI group; n=68) < or =15 mm in diameter on conventional MRI and DWI were selected from 582 consecutive patients with acute ischemic stroke. Sex, age, neurological symptoms, vascular risk factors, emboligenic heart disease, arterial occlusive disease in the ipsilateral carotid system, and recurrent stroke within the initial 30 days were compared between the 2 groups. RESULTS: Only 47% of SCOIs but 87% of SBGIs could be identified with the use of conventional MRI, whereas DWI could detect them all. Age, sex, and vascular risk factors were not significantly different between the 2 groups. The SCOI group had more frequently an abrupt onset of symptoms (63% versus 26%; P=0.0002), emboligenic heart diseases (34% versus 12%; P=0.0054), occlusive carotid and/or middle cerebral artery diseases (53% versus 19%; P=0.0004), and recurrent stroke (13% versus 1%; P=0.0216) but less frequently a classic lacunar syndrome (50% versus 81%; P=0.0009) than the SBGI group. On a multivariate analysis, both arterial and heart diseases were independently associated with the SCOI group. CONCLUSIONS: Symptomatic SCOIs detected by DWI may be associated with large-vessel and heart diseases and should be distinguished from lacunar infarcts.

Age Factors↗

Use of diffusion-weighted magnetic resonance imaging in empyema after cranioplasty.

External decompression can be an effective treatment for acute intracranial hypertension, but the cranial defect must be repaired. The most serious complication of cranioplasty is late infection. Confusing an empyema that occurs after cranioplasty with a fluid collection (haematoma or liquor) can have catastrophic consequences, such as the development of cerebritis. The goal of this study was to assess the ability of diffusion-weighted (DW) magnetic resonance imaging (MRI) to diagnose empyema after cranioplasty. DW MRI and apparent diffusion coefficient (ADC) maps were studied in six patients with surgically verified empyema after cranioplasty. The findings were compared with those in five patients who had surgically verified haematoma or liquorrhoea. In the patients with empyema, the lesion was hyperintense, whereas the fluid collections (haematoma and liquorrhoea) were visualized as hypointense lesions. The ADC maps showed that empyema had a significantly lower intensity than the fluid collections (haematoma or liquorrhoea). DW MRI can be used to identify empyema after cranioplasty and can help to differentiate it from other fluid collections. Hence, this is a useful additional imaging modality for the diagnosis of empyema after cranioplasty.

Adolescent↗

Nonrigid registration of 3D tensor medical data.

New medical imaging modalities offering multi-valued data, such as phase contrast MRA and diffusion tensor MRI, require general representations for the development of automated algorithms. In this paper we propose a unified framework for the registration of medical volumetric multi-valued data using local matching. The paper extends the usual concept of similarity between two pieces of data to be matched, commonly used with scalar (intensity) data, to the general tensor case. Our approach to registration is based on a multiresolution scheme, where the deformation field estimated in a coarser level is propagated to provide an initial deformation in the next finer one. In each level, local matching of areas with a high degree of local structure and subsequent interpolation are performed. Consequently, we provide an algorithm to assess the amount of structure in generic multi-valued data by means of gradient and correlation computations. The interpolation step is carried out by means of the Kriging estimator, which provides a novel framework for the interpolation of sparse vector fields in medical applications. The feasibility of the approach is illustrated by results on synthetic and clinical data.

Algorithms↗

Prognostication of recovery in patients with acute ischemic stroke through the use of brain SPECT with Technetium-99m--labeled metronidazole.

BACKGROUND AND PURPOSE: We hypothesized that technetium-99m-ethylene dicysteine-metronidazole (99mTc-EC-MN) localizes to brain tissue that is hypoxic but viable. This study prospectively evaluated the relationship between neurological outcome and uptake of 99mTc-EC-MN in peri-infarcted regions of the brain. METHODS: Eight patients with acute ischemic stroke in the territory of the left middle cerebral artery underwent 99mTc-EC-MN and 99mTc-ethyl cysteinate dimer (ECD) brain SPECTs on the same day during the subacute stage (10.3+/-2.5 days). The infarct volumes from 99mTc-ECD images (IV(ECD)), infarct volumes from diffusion-weighted MRI images (IV(DW)), and hypoxic volume (HV) from 99mTc-EC-MN images were calculated. The net infarct volume (NIV(ECD)) was defined as IV(ECD) minus HV. The National Institutes of Health Stroke Scale scores were measured on admission and days 1, 3, 7, and 30. RESULTS: IV(ECD) was greater than IV(DW). The lesion-to-normal count-density ratios of 99mTc-EC-MN ranged from 1.80 to 5.96. HV was 60.2+/-65.2 cm3, and the mean percent HV was 24.5+/-28.1% of IV(ECD). NIV(ECD) was 162.6+/-133.4 cm3 and was significantly smaller than IV(ECD). NIV(ECD) was significantly correlated with National Institutes of Health Stroke Scale score at 1 month and was a significant predictor of neurological deficit at 1 month. CONCLUSIONS: 99mTc-EC-MN brain SPECT can detect hypoxic tissue after acute ischemic stroke and, in combination with 99mTc-ECD brain SPECT, is useful in predicting neurological outcome in ischemic stroke patients.

Acute Disease↗

Reversal of early diffusion-weighted magnetic resonance imaging abnormalities does not necessarily reflect tissue salvage in experimental cerebral ischemia.

BACKGROUND AND PURPOSE: Diffusion-weighted MRI (DWI) can detect early ischemic changes and is sometimes used as a surrogate neurological end point in clinical trials. Recent experimental stroke studies have shown that with brief periods of ischemia, some DWI lesions transiently reverse, only to recur later. This study examined the histological condition of the tissue during the period of DWI reversal. METHODS: Rats underwent 30 minutes of middle cerebral artery occlusion followed by reperfusion. DWI images were obtained during ischemia and 3 to 5 hours, 1 day, and 7 days later. MRI scans were compared with histology (5 hours, n=5; 7 days, n=5) with the use of neuronal (microtubule-associated protein 2 [MAP2]) and astrocytic (glial fibrillary acidic protein [GFAP]) markers and heat-shock protein 72 (HSP72). RESULTS: DWI abnormalities reversed 3 to 5 hours after ischemia onset but recurred at 1 day. Four animals showed complete reversal of the initial DWI hyperintensity, and 6 showed partial reversal. When the 5-hour DWI was completely normal, there was significant loss of MAP2 immunoreactivity, comprising approximately 30% of the initial DWI lesion. However, GFAP staining revealed morphologically normal astrocytes. HSP72 immunoreactivity at 5 hours was extensive and corresponded to the initial DWI lesion. CONCLUSIONS: After brief ischemic periods, normalization of the DWI does not necessarily imply that the tissue is normal. Neurons already exhibit evidence of structural damage and stress. Normal GFAP staining suggests that other nonneuronal cell populations may partially compensate for altered fluid balances at the time of DWI reversal despite the presence of neuronal injury. These observations suggest that caution is warranted when relying solely on DWI for assessment of ischemic damage.

Animals↗

Tractography-based quantitation of diffusion tensor imaging parameters in white matter tracts of preterm newborns.

PURPOSE: To evaluate the feasibility of performing diffusion tensor tractography (DTT) to map and quantify the pyramidal white matter tracts of premature newborns. MATERIALS AND METHODS: Fourteen diffusion tensor MRI (DTI) examinations of nine premature newborns were evaluated. DTT was performed to segment bilateral pyramidal tracts, using a fiber-tracking algorithm originating in the cerebral peduncle (CP) and filtering through the posterior limb of the internal capsule (PLIC) and precentral gyrus (PCG). Voxels containing the resulting tracts were then used for quantitation of DTI parameters along the tract. The DTT-based tract measurements were compared with standard manually placed region-of-interest (ROI) measurements at four locations along the pyramidal tract, and the reproducibility of each technique was evaluated. RESULTS: DTT demonstrated improved reproducibility over manual ROI measurement for pyramidal tract quantitation and was less subject to intra-operator variability (P < 0.0001, Fisher test for equal variance). In general, the anatomic locations and measurements obtained with the two techniques were in good agreement, although some systematic differences were identified in the PLIC and CP. CONCLUSION: Fiber DTT is feasible in premature newborns, provides more reproducible tract measurements than manual ROI methods, and allows quantitation along the entire tract for more detailed DTI assessment of white matter maturation.

Diffusion Magnetic Resonance Imaging↗

[Leptomeningeal abnormality on Gd-DTPA enhanced MRI in a case of SLE presenting diffuse organic brain syndrome].

Involvement of the central nervous system associated with SLE (CNS lupus) is not rare. Two types of CNS lupus are noted clinically; one group manifesting focal neurological symptoms and another group showing mental symptoms. Though it is well known that neurological symptoms are caused by arteritis and thrombus, pathophysiological mechanisms leading to mental symptoms remain obscure and there is no established clinical evidence responsible for these symptoms. A 41-year-old woman was confused and her attention was markedly impaired. Her mental symptoms consisted of disorientation, restlessness, euphoria and emotional incontinence. There were neither focal neurological signs nor meningeal signs. Cerebrospinal fluid (CSF) examination showed increased number of polymorphonuclear cells and permeability of the blood-brain barrier, calculated based on the CSF/plasma protein ratio, was also elevated. Repeated bacteriological examinations revealed to be negative. Gd-DTPA MRI demonstrated diffuse enhancement of the cerebral leptomeninges. Methylprednisolone pulse therapy ameliorated her mental deterioration effectively, and subsequently the leptomeningeal enhancement with Gd-DTPA MRI disappeared in parallel. These radiological and laboratory findings suggest that SLE itself causes inflammation of vessels in the leptomeninges and adjacent cerebral cortex. We consider mental symptoms associated with SLE may be caused, at least in part, by this mechanism. To our knowledge, we could not find similar reports in the literature. Gd-DTPA enhanced MRI seems to be of clinical use for making diagnosis, evaluating clinical activity and understanding of CNS lupus.

Adult↗

Silent cerebral ischemia detected with diffusion-weighted imaging in patients treated with protected and unprotected carotid artery stenting.

BACKGROUND AND PURPOSE: Percutaneous transluminal angioplasty with stent (CAS) is an alternative method to endarterectomy in the revascularization of carotid artery stenosis. Protected CAS is currently used to prevent distal embolization. Diffusion-weighted MRI (DWI) is the most sensitive tool to evaluate silent cerebral ischemia. The purpose of this research was to assess the incidence of cerebral embolic lesions during CAS and to evaluate whether cerebral protection devices can reduce the number of silent cerebral ischemia with respect to unprotected CAS. METHODS: Fifty-two patients with high-grade internal stenosis underwent CAS; 30 patients (group a) were treated with a cerebral protection device, and 22 (group b) were treated without it. All of the patients were evaluated preoperatively and postoperatively with fluid-attenuated inversion recovery and DWI sequences to depict the number of new embolic silent cerebral lesions. RESULTS: Embolic silent cerebral lesions occurred in 30% of CAS. Cerebral protection devices reduce the number of new lesions significantly reducing the consistent lesions ipsilateral to the treated vessel. Inconsistent lesions do not differ in both groups of patients. Clinical, radiological, and procedural variables do not correlate with the appearance of new cerebral lesions. CONCLUSIONS: Embolic cerebral lesions detected with DWI are more frequent with unprotected CAS, although they are present also with the use of cerebral protection devices. Probably a part of silent cerebral lesions arise from the procedural maneuver in the aortic arch.

Aged↗