Wu O, Østergaard L, Weisskoff RM, Benner T, Rosen BR, Sorensen GA. Tracer arrival timing-insensitive technique for estimating flow in MR perfusion-weighted imaging using singular value decomposition with a block-circulant deconvolution matrix. Magn Reson Med 2003;50(1):164-74.Abstract
    Relative cerebral blood flow (CBF) and tissue mean transit time (MTT) estimates from bolus-tracking MR perfusion-weighted imaging (PWI) have been shown to be sensitive to delay and dispersion when using singular value decomposition (SVD) with a single measured arterial input function. This study proposes a technique that is made time-shift insensitive by the use of a block-circulant matrix for deconvolution with (oSVD) and without (cSVD) minimization of oscillation of the derived residue function. The performances of these methods are compared with standard SVD (sSVD) in both numerical simulations and in clinically acquired data. An additional index of disturbed hemodynamics (oDelay) is proposed that represents the tracer arrival time difference between the AIF and tissue signal. Results show that PWI estimates from sSVD are weighted by tracer arrival time differences, while those from oSVD and cSVD are not. oSVD also provides estimates that are less sensitive to blood volume compared to cSVD. Using PWI data that can be routinely collected clinically, oSVD shows promise in providing tracer arrival timing-insensitive flow estimates and hence a more specific indicator of ischemic injury. Shift maps can continue to provide a sensitive reflection of disturbed hemodynamics.
    van Osch MJ, Vonken E-JPA, Wu O, Viergever MA, van der Grond J, Bakker CJG. Model of the human vasculature for studying the influence of contrast injection speed on cerebral perfusion MRI. Magn Reson Med 2003;50(3):614-22.Abstract
    Simulations of dynamic susceptibility contrast (DSC) MRI are frequently performed by assuming a certain shape for the input function and the microvascular response function. However, to investigate the influence of parameters that will affect the shape of the input function, a more complex model of the human vasculature is required. In this study, a model of the human vasculature is proposed that consists of a network of vascular operators based on physiological data typical of a 35-year-old male subject. The simulated contrast passage curves were found to be within the range of observed contrast passage curves in a population of patients without vascular disease. The model was used to predict the effect of different injection speeds of the contrast agent on the accuracy of the perfusion experiment. It was found that injection speeds of <3 ml/s lead to an underestimation of the observed cerebral blood flow (CBF). Additionally, it was determined that decreasing the temporal resolution of the acquisition results in an underestimation of the CBF values, and an increase of the standard deviation (SD) of CBF measurements.
    Yamada K, Wu O, Gonzalez GR, Bakker D, Østergaard L, Copen WA, Weisskoff RM, Rosen BR, Yagi K, Nishimura T, Sorensen GA. Magnetic resonance perfusion-weighted imaging of acute cerebral infarction: effect of the calculation methods and underlying vasculopathy. Stroke 2002;33(1):87-94.Abstract
    BACKGROUND AND PURPOSE: Various calculation methods are available to estimate the transit-time on MR perfusion-weighted imaging (PWI). Each method may affect the results of PWI. Steno-occlusive disease in the parent vessels is another factor that may affect the results of the PWI. The purpose of this study was to elucidate the effect of the calculation methods and underlying vasculopathy on PWI. METHODS: From a pool of 113 patients who had undergone PWI during the study period, a total of 12 patients with nonlacunar ischemic strokes who were scanned within 24 hours after onset of symptom were selected for the study. The patient population consisted of 6 patients who had extracranial internal carotid artery stenosis (>70%) and 6 individuals without stenosis. Seven different postprocessing methods were evaluated: first moment, ratio of area to peak, time to peak (TTP), relative TTP, arrival time, full-width at half-maximum, and deconvolution methods. Follow-up MR or CT images were used to determine the areas that evolved into infarcts, which served as the gold standard. Sensitivity and specificity of each transit time technique were calculated. RESULTS: Calculation methods with high sensitivity were the first moment (sensitivity, 74%), TTP (sensitivity, 77%), and deconvolution methods (sensitivity, 81% to 94%). Between the 2 groups with and without internal carotid artery stenosis, the specificity of most of the techniques was lower in the internal carotid artery stenosis group. The first moment and deconvolution methods maintained relatively high specificity even in the stenosis group. CONCLUSIONS: The calculation technique and presence of underlying vasculopathy have a direct impact on the results of PWI. The methods with high sensitivity even in the presence of steno-occlusive disease were the first moment and deconvolution methods with arterial input function derived from the peri-infarct arteries; the deconvolution method was the superior choice because of higher lesion conspicuity.
    Dijkhuizen RM, Asahi M, Wu O, Rosen BR, Lo EH. Rapid breakdown of microvascular barriers and subsequent hemorrhagic transformation after delayed recombinant tissue plasminogen activator treatment in a rat embolic stroke model. Stroke 2002;33(8):2100-4.Abstract
    BACKGROUND AND PURPOSE: Thrombolytic therapy with recombinant tissue plasminogen activator (rtPA) after stroke increases risk of hemorrhagic transformation, particularly in areas with blood-brain barrier leakage. Our aim was to characterize acute effects of rtPA administration on the integrity of microvascular barriers. METHODS: Stroke was induced in spontaneously hypertensive rats by unilateral embolic middle cerebral artery occlusion. Six hours after stroke, rtPA was intravenously administered (n=10). Controls received saline (n=4). Extravasation of the large-diameter contrast agent monocrystalline iron oxide nanocolloid (MION) was assessed with susceptibility contrast-enhanced MRI during rtPA injection. In addition, we performed perfusion MRI and diffusion-weighted MRI. After MRI, 2 hours after rtPA treatment, intracerebral hemorrhage was quantified with a spectrophotometric hemoglobin assay. RESULTS: Late rtPA treatment resulted in increased hemorrhage volume (8.4+/-1.7 versus 2.9+/-0.9 micro L in controls; P<0.05). In MION-injected animals, during rtPA administration, transverse relaxation rate change (DeltaR2*) increased from 12.4+/-6.0 to 31.6+/-19.2 s(-1) (P<0.05) in areas with subsequent hemorrhage. Significant DeltaR2* changes were absent in nonhemorrhagic areas, in animals without injected MION, and in saline-treated animals. Thrombolytic therapy did not improve perfusion in regions with hemorrhagic transformation (cerebral blood flow index was 22.8+/-19.7% [of contralateral] at 0.5 hours before and 22.4+/-18.0% at 1 hour after rtPA administration). CONCLUSIONS: The DeltaR2* changes during rtPA delivery in MION-injected animals indicate extravasation of MION, which reflects increased permeability of the blood-brain barrier. This implies that late rtPA treatment rapidly aggravates early ischemia-induced damage to microvascular barriers, thereby enhancing hemorrhagic transformation.
    Wu O, Koroshetz WJ, Ostergaard L, Buonanno FS, Copen WA, Gonzalez RG, Rordorf G, Rosen BR, Schwamm LH, Weisskoff RM, Sorensen AG. Predicting tissue outcome in acute human cerebral ischemia using combined diffusion- and perfusion-weighted MR imaging. Stroke 2001;32(4):933-42.Abstract
    BACKGROUND AND PURPOSE: Tissue signatures from acute MR imaging of the brain may be able to categorize physiological status and thereby assist clinical decision making. We designed and analyzed statistical algorithms to evaluate the risk of infarction for each voxel of tissue using acute human functional MRI. METHODS: Diffusion-weighted MR images (DWI) and perfusion-weighted MR images (PWI) from acute stroke patients scanned within 12 hours of symptom onset were retrospectively studied and used to develop thresholding and generalized linear model (GLM) algorithms predicting tissue outcome as determined by follow-up MRI. The performances of the algorithms were evaluated for each patient by using receiver operating characteristic curves. RESULTS: At their optimal operating points, thresholding algorithms combining DWI and PWI provided 66% sensitivity and 83% specificity, and GLM algorithms combining DWI and PWI predicted with 66% sensitivity and 84% specificity voxels that proceeded to infarct. Thresholding algorithms that combined DWI and PWI provided significant improvement to algorithms that utilized DWI alone (P=0.02) but no significant improvement over algorithms utilizing PWI alone (P=0.21). GLM algorithms that combined DWI and PWI showed significant improvement over algorithms that used only DWI (P=0.02) or PWI (P=0.04). The performances of thresholding and GLM algorithms were comparable (P>0.2). CONCLUSIONS: Algorithms that combine acute DWI and PWI can assess the risk of infarction with higher specificity and sensitivity than algorithms that use DWI or PWI individually. Methods for quantitatively assessing the risk of infarction on a voxel-by-voxel basis show promise as techniques for investigating the natural spatial evolution of ischemic damage in humans.
    Yoshiura T, Wu O, Sorensen AG. Advanced MR techniques: diffusion MR imaging, perfusion MR imaging, and spectroscopy. Neuroimaging Clin N Am 1999;9(3):439-53.Abstract
    Recent technical advances in MR imaging have enabled the authors to investigate early physiological changes in acute ischemic stroke lesion. Diffusion and perfusion MR imaging can provide clinically useful information not only for early detection of ischemia, but also for prediction of tissue outcome. MR spectroscopy is a potentially powerful tool to study acute stroke, but its clinical value has been limited due to long examination time and low spatial resolution.
    Sanchez Del Rio M, Bakker D, Wu O, Agosti R, Mitsikostas DD, Ostergaard L, Wells WA, Rosen BR, Sorensen G, Moskowitz MA, Cutrer FM. Perfusion weighted imaging during migraine: spontaneous visual aura and headache. Cephalalgia 1999;19(8):701-7.Abstract
    Using perfusion weighted imaging, we studied 28 spontaneous migraine episodes; 7 during visual aura (n = 6), 7 during the headache phase following visual aura (n = 3), and 14 cases of migraine without aura (n = 13). The data were analyzed using a region-of-interest-based approach. During aura, relative cerebral blood flow (rCBF) was significantly decreased (27% +/- 0.07) in occipital cortex contralateral to the affected hemifield. rCBV was decreased (15% +/- 0.12) and mean transit time increased (32% +/- 0.3), persisting up to 2.5 h into the headache phase. Other brain regions did not show significant perfusion changes. During migraine without aura, no significant hemodynamic changes were observed. In one patient who experienced both migraine with and without aura, perfusion deficits were observed only during migraine with aura. These findings suggest that decremental blood flow changes in occipital lobe are most characteristic of migraine with aura.