Biomedical subjects

Hannu J Aronen

Publications and source records attributed to Hannu J Aronen.

At least 19 recordsLinked to original sources

PubMed2006

The real estate factor: quantifying the impact of infarct location on stroke severity.

BACKGROUND AND PURPOSE: The severity of the neurological deficit after ischemic stroke is moderately correlated with infarct volume. In the current study, we sought to quantify the impact of location on neurological deficit severity and to delineate this impact from that of volume. METHODS: We developed atlases consisting of location-weighted values indicating the relative importance in terms of neurological deficit severity for every voxel of the brain. These atlases were applied to 80 first-ever ischemic stroke patients to produce estimates of clinical deficit severity. Each patient had an MRI and National Institutes of Health Stroke Scale (NIHSS) examination just before or soon after hospital discharge. The correlation between the location-based deficit predictions and measured neurological deficit (NIHSS) scores were compared with the correlation obtained using volume alone to predict the neurological deficit. RESULTS: Volume-based estimates of neurological deficit severity were only moderately correlated with measured NIHSS scores (r=0.62). The combination of volume and location resulted in a significantly better correlation with clinical deficit severity (r=0.79, P=0.032). CONCLUSIONS: The atlas methodology is a feasible way of integrating infarct size and location to predict stroke severity. It can estimate stroke severity better than volume alone.

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PubMed2006

Sensorimotor cortex localization: comparison of magnetoencephalography, functional MR imaging, and intraoperative cortical mapping.

PURPOSE: To prospectively evaluate magnetoencephalography (MEG) and functional magnetic resonance (MR) imaging, as compared with intraoperative cortical mapping, for identification of the central sulcus. MATERIALS AND METHODS: Fifteen patients (six men, nine women; age range, 25-58 years) with a lesion near the primary sensorimotor cortex (13 gliomas, one cavernous hemangioma, and one meningioma) were examined after institutional review board approval and written informed consent from each patient were obtained. At MEG, evoked magnetic fields to median nerve stimulation were recorded; at functional MR imaging, hemodynamic responses to self-paced palmar flexion of the wrist were imaged. General linear model analysis with contextual clustering (P < .01) was used to analyze functional MR imaging data, and dipole modeling was used to analyze MEG data. MEG and functional MR localizations were compared with intraoperative cortical mappings. The distance from the area of functional MR imaging activation to the tumor margin was compared between the patients with discordant and those with concordant intraoperative mapping findings by using unpaired t testing. RESULTS: MEG depicted the central sulcus correctly in all 15 patients, as verified at intraoperative mapping. The functional MR imaging localization results agreed with the intraoperative mappings in 11 patients. In all four patients with a false localization, the primary activation was in the postcentral sulcus region, but it did not differ significantly from the primary activation in the patients with correct localization with respect to proximity to the tumor (P = .38). Furthermore, at functional MR imaging, multiple nonprimary areas were activated, with considerable interindividual variation. CONCLUSION: Although both MEG and functional MR imaging can provide useful information for neurosurgical planning, in the present study, MEG proved to be superior for locating the central sulcus. Activation of multiple nonprimary cerebral areas may confound the interpretation of functional MR imaging results.

Adult↗

PubMed2006

Acute opioid effects on human brain as revealed by functional magnetic resonance imaging.

Functional magnetic resonance imaging has been widely used to study brain activation induced either by specific sensory stimulation or motor or cognitive task performance. We demonstrate that functional magnetic resonance imaging can provide information of brain regions involved in opioid-induced central nervous system effects. The reproducibility of the responses in the predefined regions of interest was confirmed by repeated boluses of ultra-short acting mu-opioid receptor agonist remifentanil and saline. We report spatially and temporally detailed information after remifentanil administration. Areas rich in mu-opioid receptors showed strong activations, whereas primary somatosensory cortex that has the lowest density of mu-opioid receptors showed negligible activation. The cingulate, orbitofrontal, posterior parietal and insular cortices, and amygdala showed activation, which was temporally closely related to most subjective sensations that were strongest at 80 to 90 s after drug administration. These areas belong to a circuitry that modulates the affective experience of sensory stimuli.

Adult↗

PubMed2005

Cine MR imaging of myocardial contractile impairment in patients with hypertrophic cardiomyopathy attributable to Asp175Asn mutation in the alpha-tropomyosin gene.

PURPOSE: To prospectively investigate the relationship between myocardial contractile impairment and left ventricular (LV) hypertrophy measured at cardiac magnetic resonance (MR) imaging in patients with hypertrophic cardiomyopathy (HCM) caused by the substitution of aspartic acid 175 with asparagine (ie, Asp175Asn mutation) in the alpha-tropomyosin gene (TPM1). MATERIALS AND METHODS: The study protocol was approved by the hospital ethics committee, and all subjects gave written informed consent. LV mass, maximal LV wall thickness, and myocardial fractional thickening during systole were measured at cine MR imaging in 24 subjects (11 male, 13 female; mean age, 42 years; age range, 17-68 years) with the Asp175Asn mutation in TPM1 and in 17 healthy volunteers (eight men, nine women; mean age, 38 years; age range, 23-60 years). The proportion of hypokinetic LV segments was calculated as the number of LV segments with fractional thickening of less than 30% divided by the total number of segments measured. Anthropometric and biochemical correlates of LV hypertrophy were determined. Univariate and multiple linear regression analyses were used to investigate the association of the proportion of hypokinetic segments and other correlates of LV hypertrophy with LV mass and maximal wall thickness. RESULTS: The proportion of hypokinetic segments was higher in patients with HCM than in control subjects (37% +/- 20 [standard deviation] vs 12% +/- 12, P < .001). In stepwise multiple regression analysis, the proportion of hypokinetic segments accounted for 42% (P < .001); the LV end-diastolic volume, for 24% (P = .003); and male sex, for 10% (P = .014) of the variability in LV mass in patients with HCM. The proportion of hypokinetic LV segments, which accounted for 48% of the variability in LV maximal wall thickness (P < .001), was the only variable significantly associated with maximal wall thickness. CONCLUSION: The extent of myocardial contractile impairment is strongly and independently related to LV mass and maximal wall thickness in patients with HCM attributable to the Asp175Asn mutation in TPM1.

Adult↗

PubMed2005

Cortical generators of slow evoked responses elicited by spatial and nonspatial auditory working memory tasks.

OBJECTIVE: Slow evoked responses have been extensively studied using electrophysiological and neuroimaging methods, but there is no consensus regarding their generators. We investigated the generators of the P3 and positive slow wave (PSW) in the evoked responses to probes recorded during auditory working memory tasks to find out whether there is dissociation between functional networks involved in the generation of the P3 and PSW and between spatial and nonspatial auditory processing within this time window. METHODS: Whole-head magneto-(MEG) and electroencephalography (EEG); analysis of MEG data using minimum-norm current estimates. RESULTS: The associative temporal, occipito-temporal and parietal areas contributed to the generation of the slow evoked responses. The temporal source increased while the occipito-temporal source diminished activity during transition from the P3 to PSW. The occipito-temporal generator of the P3 was activated more during the spatial than nonspatial task, and the left temporal generator of the PSW tended to be more strongly activated during the nonspatial task. CONCLUSIONS: These findings indicate that partially distinct functional networks generate the P3 and PSW and provide evidence for segregation of spatial and nonspatial auditory information processing in associative areas beyond the supratemporal auditory cortex. SIGNIFICANCE: The present results support the dual-stream model for auditory information processing.

Acoustic Stimulation↗

PubMed2005

Distinct and overlapping fMRI activation networks for processing of novel identities and locations of objects.

The ventral visual stream processes information about the identity of objects ('what'), whereas the dorsal stream processes the spatial locations of objects ('where'). There is a corresponding, although disputed, distinction for the ventrolateral and dorsolateral prefrontal areas. Furthermore, there seems to be a distinction between the anterior and posterior medial temporal lobe (MTL) structures in the processing of novel items and new spatial arrangements, respectively. Functional differentiation of the intermediary mid-line cortical and temporal neocortical structures that communicate with the occipitotemporal, occipitoparietal, prefrontal, and MTL structures, however, is unclear. Therefore, in the present functional magnetic resonance imaging (fMRI) study, we examined whether the distinction among the MTL structures extends to these closely connected cortical areas. The most striking difference in the fMRI responses during visual presentation of changes in either items or their locations was the bilateral activation of the temporal lobe and ventrolateral prefrontal cortical areas for novel object identification in contrast to wide parietal and dorsolateral prefrontal activation for the novel locations of objects. An anterior-posterior distinction of fMRI responses similar to the MTL was observed in the cingulate/retrosplenial, and superior and middle temporal cortices. In addition to the distinct areas of activation, certain frontal, parietal, and temporo-occipital areas responded to both object and spatial novelty, suggesting a common attentional network for both types of changes in the visual environment. These findings offer new insights to the functional roles and intrinsic specialization of the cingulate/retrosplenial, and lateral temporal cortical areas in visuospatial cognition.

Adult↗

PubMed2004

Abnormal intravoxel cerebral blood flow heterogeneity in human ischemic stroke determined by dynamic susceptibility contrast magnetic resonance imaging.

BACKGROUND AND PURPOSE: The determination of cerebral blood flow heterogeneity (FH) by dynamic susceptibility contrast (DSC) magnetic resonance imaging has recently been proposed as a tool to predict final infarct size in acute stroke. In this study, we describe the evolution of FH during the first week as well as its correlation to the patients' clinical status. METHODS: Ten patients with ischemic stroke were studied with DSC MRI and diffusion-weighted imaging in hyperacute (<6 hours) phase, at 24 hours, and 1 week after symptom onset. In addition to intravoxel FH, cerebral blood volume (CBV), cerebral blood flow (CBF), and contrast agent mean transit time (MTT) were determined from DSC MRI. All patients were evaluated neurologically with National Institute of Health Stroke Scale concurrently with the imaging sessions. RESULTS: All patients showed infarct growth, judged by diffusion-weighted imaging, during the week with simultaneous decrease in the sizes of FH, CBV, CBF, and MTT abnormalities. The FH abnormality was shown to be larger than CBV and CBF abnormalities at the hyperacute phase and 24 hours, but smaller than MTT abnormality in all 3 imaging sessions. The sizes of hyperacute FH, CBV, CBF, and MTT abnormalities correlated well with infarct size at 24 hours and at 1 week. Additionally, FH was the only perfusion parameter that correlated with the clinical score. CONCLUSIONS: FH predicts infarct size equally well with the other perfusion parameters but is superior in correlation with the clinical score. FH can easily be incorporated to hyperacute stroke imaging without additional efforts.

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PubMed2004

MRI volumetry of the vermis and the cerebellar hemispheres in men with schizophrenia.

An association between cerebellar abnormalities and different manifestations of schizophrenia is increasingly hypothesized, either at the motor (anterior vermis), affective/psychotic (posterior vermis), or cognitive (cerebellar hemispheres) level. However, morphometric and volumetric cerebellar measurements have yielded highly divergent results. The main goal of this study was to use magnetic resonance imaging (MRI) to separately estimate the volumes of the entire vermis, the cerebellar hemispheres and three midsaggital vermian areas among 38 men with schizophrenia and 26 healthy men. Compared with the control group, persons with schizophrenia had significantly smaller volumes of the whole vermis, but not of the cerebellar hemispheres, a difference that approached significance when only the patients without a comorbid diagnosis of alcohol abuse/dependence were considered. Significant anomalies of the posterior vermian areas (lobules VI and VII) were detected in both subgroups of patients, while abnormalities of the anterior vermis (lobules I-V) were observed only among patients with a dual diagnosis of alcoholism. No difference emerged between the groups at the inferior vermian level (lobules VIII-X). Overall, these findings corroborate the hypothesized association between schizophrenia and specific posterior vermian anomalies, which might not necessarily be the consequence of alcohol abuse. However, the suggestion that schizophrenia is related to abnormal volumes of the lateral cerebellum is not supported.

Adult↗

PubMed2004

Acute ischemic stroke: predictive value of 2D phase-contrast MR angiography--serial study with combined diffusion and perfusion MR imaging.

PURPOSE: To evaluate phase-contrast magnetic resonance (MR) angiography and diffusion- and perfusion-weighted imaging in predicting evolution of infarction and clinical outcome. MATERIALS AND METHODS: Phase-contrast angiographic and diffusion-weighted images obtained 1 and 2 days after acute middle cerebral artery (MCA) stroke were assessed in 43 patients; 39 underwent perfusion-weighted imaging on day 1. Follow-up phase-contrast angiographic and T2-weighted images (n = 38) were obtained on day 8. Clinical outcome was assessed at 3 months. Patients were assigned to three groups according to angiographic findings on day 1: group 1, absence of flow in proximal MCA (M1 segment); group 2, internal carotid artery (ICA) occlusion with collateral M1 flow; group 3, flow in ICA and M1. Differences in lesion volumes on diffusion- and perfusion-weighted maps among groups were compared with one-way analysis of variance with Tukey post hoc multiple comparisons. RESULTS: Patients in group 1 had significantly larger infarct growth, volumes of hypoperfusion on relative cerebral blood volume (rCBV) and relative cerebral blood flow maps, and initial and final infarct volumes than did other patients (P <.05). Initial perfusion deficits on mean transit time maps were significantly (P =.002) larger in group 2 than in group 3, but there were no significant differences in infarct growth (P =.977), final infarct volume on day 8 (P =.947), and clinical outcome (P =.969). Absence of M1 flow on day 1 was significantly associated with unfavorable clinical outcome (modified Rankin score > or = 3) at 3 months (P =.010, chi(2) test). Discriminant analysis revealed that rCBV maps alone and combination of diffusion-weighted imaging and MR angiography yielded the highest accuracy in predicting an unfavorable clinical outcome. CONCLUSION: Phase-contrast MR angiography can provide complementary information to that with diffusion- and perfusion- weighted imaging in predicting the outcome of patients with acute stroke.

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PubMed2004

Visual presentation of novel objects and new spatial arrangements of objects differentially activates the medial temporal lobe subareas in humans.

A number of studies in rodents and monkeys report a distinction between the contributions of the hippocampus and perirhinal cortex to memory, such that the hippocampus is crucial for spatial memory whereas the perirhinal cortex has a pivotal role in perception and memory for visual objects. To determine if there is such a distinction in humans, we conducted a functional magnetic resonance imaging study to compare the medial temporal lobe responses to changes in object identity and spatial configurations of objects. We found evidence for the predicted distinction between hippocampal and perirhinal cortical activations, although part of the hippocampus was also activated by identification of novel objects. Additionally, an anterior-posterior activation gradient emerged inside the hippocampus and parahippocampal cortex. The anterior hippocampus, perirhinal cortex and anterior parahippocampal cortex are involved in perception of contextually novel objects, whereas the posterior hippocampus and posterior parahippocampal cortex are involved in processing of novel arrangements of familiar objects. These results demonstrate that there is a functional dissociation between processing of novel object identities and new spatial locations of objects among the subregions of medial temporal lobe structures in humans also.

Adult↗

PubMed2003

Encoding of novel picture pairs activates the perirhinal cortex: an fMRI study.

It is well established in nonhuman primates that the medial temporal lobe (MTL) structures, the hippocampus and the entorhinal and perirhinal cortices, are necessary for declarative memory encoding. In humans, the neuropathological and neuropsychological changes in early Alzheimer's disease (AD) further support a role for the rhinal cortex in the consolidation of new events into long-term memory. Little is known, however, regarding the function of the rhinal cortex in humans in vivo. To examine the participation of the interconnected MTL structures as well as the whole-brain network of activated brain areas in visual associative long-term memory, functional magnetic resonance imaging (fMRI) was used to determine the brain regions that are activated during encoding and retrieval of paired pictures in 12 young control subjects. The most striking finding in the MTL activation pattern was the consistent activation of the perirhinal cortex in the encoding-baseline and encoding-retrieval comparisons with a strict statistical threshold (P < 0.00001). In contrast, no perirhinal cortex activation was detected in the retrieval-baseline or retrieval-encoding comparisons even with a low statistical threshold (P < 0.05). The location of the perirhinal activation area was in the transentorhinal part of the perirhinal cortex, in the medial bank of the collateral sulcus. The hippocampus and the more posterior parahippocampal gyrus were activated in both encoding and retrieval conditions. During the encoding processing, MTL activations were more consistent and the hippocampal activation area located more anteriorly than during retrieval. The frontal, parietal, temporal, and occipital association cortices were also activated in the encoding-baseline and retrieval-baseline comparisons. The data suggest that encoding, but not retrieval, of novel picture pairs activates the perirhinal cortex. To our knowledge, this is the first fMRI study reporting encoding activation in this transentorhinal part of the perirhinal cortex, the site of the very earliest neuropathological changes in AD.

Adult↗

PubMed2003

Differences between auditory evoked responses recorded during spatial and nonspatial working memory tasks.

Results from several recent studies suggest that neuronal processing of sound content and its spatial location may be dissociated. The use of modern neuroimaging techniques has allowed for the determination that different brain structures may be specifically activated during working memory processing of pitch and location of sound. The time course of these task-related differences, however, remains uncertain. In the present study, we performed simultaneous whole-head electroencephalogram and magnetoencephalogram recordings, using a new behavioral paradigm, to investigate the dynamics of differences between "what" and "where" evoked responses in the auditory system as a function of memory load. In the location task the latency of the N1m was shorter and its generator was situated more inferiorly than in the pitch task. Working memory processing of the tonal frequency enhanced the amplitude of the N2 component, as well as the negative-going deflection at a latency around 400 ms. A memory-load-dependent task-related difference was found in the positive slow wave which was higher during the location than pitch task at the low load. Late slow waves were affected by memory load but not type of task. These results suggest that separate neuronal networks are involved in the attribute-specific analysis of auditory stimuli and their encoding into working memory, whereas the maintenance of auditory information is accomplished by a common, nonspecific neuronal network.

Acoustic Stimulation↗

PubMed2003

Effects of noise from functional magnetic resonance imaging on auditory event-related potentials in working memory task.

The effects of functional magnetic resonance imaging (fMRI) acoustic noise were investigated on the parameters of event-related responses (ERPs) elicited during auditory matching-to-sample location and pitch working memory tasks. Stimuli were tones with varying location (left or right) and frequency (high or low). Subjects were instructed to memorize and compare either the locations or frequencies of the stimuli with each other. Tape-recorded fMRI acoustic noise was presented in half of the experimental blocks. The fMRI noise considerably enhanced the P1 component, reduced the amplitude and increased the latency of the N1, shortened the latency of the N2, and enhanced the amplitude of the P3 in both tasks. The N1 amplitude was higher in the location than pitch task in both noise and no-noise blocks, whereas the task-related N1 latency difference was present in the no-noise blocks only. Although the task-related differences between spatial and nonspatial auditory responses were partially preserved in noise, the finding that the acoustic gradient noise accompanying functional MR imaging modulated the auditory ERPs implies that the noise may confound the results of auditory fMRI experiments especially when studying higher cognitive processing.

Acoustic Stimulation↗

PubMed2003

Visual processing of coherent rotation in the central visual field: an fMRI study.

Functional magnetic resonance imaging was used to determine the brain areas that process coherent motion. To reduce the activity related to eye-movement planning and self-motion perception, rotation was used as coherent motion and the stimulus was restricted to the central visual field. Coherent rotation relative to incoherent random-dot motion resulted in consistent activation in the superior parietal lobule (SPL), in the lateral occipital gyrus (presumptive kinetic occipital region, KO), and in the fusiform gyrus (FG). The main novel finding in present study is the bilateral SPL activation, which has not been found in any previous study contrasting coherent and incoherent motion. It is suggested that the SPL activation is related to form-from-motion processing. The stimulus modification that prevented abrupt appearances of dots at the borders of the stimulus field increased the strength of rolling disk-like percept of the coherent stimulus. This perception of form may also be at least partly responsible for the activation in KO and FG. With this explanation, our three consistent activation areas are in line with previous findings. Furthermore, these results demonstrate that even delicate changes in some stimulus aspects can lead to significant changes in the activation of the brain.

Adult↗

PubMed2003

Wall motion and perfusion analysis of transmyocardial laser revascularization.

OBJECTIVE: Transmyocardial laser revascularization (TMLR) creates channels in the myocardium. The aim of the treatment is to relieve angina in patients with end-stage coronary artery disease. We studied the effect of TMLR on myocardial function and perfusion with the combination of cine magnetic resonance imaging (MRI) and thallium scintigraphy. DESIGN: Eight patients with severe triple-vessel coronary artery disease were studied with MRI and thallium scintigraphy before and 6 months after laser treatment. RESULTS: TMLR did not improve global left ventricular (LV) function or myocardial perfusion. However, systolic wall thickening deprived in segments with fixed perfusion defects in 6 months and laser treatment prevented this deprivation (p = 0.03). In addition single photon emission computed tomography (SPECT) imaging indicated that TMLR prevented conversion of reversible into fixed defects. CONCLUSION: In severe, progressing coronary artery disease TMLR does not improve global LV function or myocardial perfusion, but it preserves systolic wall thickening in fixed defects (scar). It also prevents changes from ischemic myocardial regions to scar.

Aged↗

PubMed2003

First-pass MR imaging in the assessment of perfusion impairment in patients with hypertrophic cardiomyopathy and the Asp175Asn mutation of the alpha-tropomyosin gene.

PURPOSE: To assess first-pass magnetic resonance (MR) imaging in the evaluation of perfusion impairment in a genetically homogeneous population of patients with hypertrophic cardiomyopathy (HCM) and the Asp175Asn mutation of the alpha-tropomyosin gene and to evaluate the association between hypertrophy and perfusion. MATERIALS AND METHODS: Rest-stress first-pass MR imaging with gadopentetate dimeglumine was performed in 17 patients with HCM and the Asp175Asn substitution in the alpha-tropomyosin gene and in five control subjects. Global and segmental first-pass reserve index (FPR) measurements were derived from signal intensity versus time curves. Left ventricular (LV) wall thickness and LV mass index were measured on cine MR images. The Mann-Whitney test was used to evaluate the difference in FPR between the patient group and the control group. The Spearman correlation was used to evaluate the association between LV hypertrophy and FPR. RESULTS: Global FPR was significantly lower in the patients with HCM than in the control subjects (1.12 +/- 0.35 vs 1.80 +/- 0.58, P =.015). In patients with HCM, maximal LV wall thickness and LV mass index correlated negatively with global FPR (r = -0.723, P =.001 and r = -0.598, P =.011, respectively). At the regional level, segmental FPR correlated inversely with LV wall thickness (r = -0.389; P <.001) in patients with HCM. CONCLUSION: First-pass MR imaging facilitates global and regional evaluation of perfusion impairment in patients with HCM. The severity of perfusion impairment is associated with the degree of LV hypertrophy.

Adenosine↗

PubMed2003

Cardiac adrenergic activity is associated with left ventricular hypertrophy in genetically homogeneous subjects with hypertrophic cardiomyopathy.

UNLABELLED: Hypertrophic cardiomyopathy (HCM) is a genetic disease caused by mutations in genes encoding sarcomeric proteins. However, other genetic and possibly also environmental factors modify the phenotypic expression of left ventricular (LV) hypertrophy. The present study investigated whether cardiac adrenergic activity affects the severity of LV hypertrophy in genetically identical patients with HCM. METHODS: The study population consisted of 21 patients with HCM caused by the Asp175Asn substitution of the alpha-tropomyosin gene (TPM1-Asp175Asn) and 9 healthy volunteers. LV mass and segmental wall thickness were measured with MRI. Presynaptic cardiac adrenergic activity was measured with (123)I-metaiodobenzylguanidine (MIBG) SPECT. Global and segmental washouts of (123)I-MIBG were calculated. RESULTS: Global myocardial (123)I-MIBG washout was faster in patients with TPM1-Asp175Asn than in healthy volunteers (50% +/- 9% vs. 37% +/- 8%, P = 0.001). In linear regression analysis, global (123)I-MIBG washout was associated with the LV mass index and LV maximal wall thickness index in HCM patients (r = 0.512, P = 0.018, and r = 0.478, P = 0.028, respectively). The mean (123)I-MIBG washout was higher in LV segments >/= 15 mm thick than in LV segments < 15 mm thick (56 +/- 10 vs. 49% +/- 10%, P = 0.002). CONCLUSION: In patients with HCM sharing the same causal gene defect, the degree of LV hypertrophy is related to (123)I-MIBG washout, suggesting that cardiac adrenergic activity modifies phenotypic expression in HCM.

3-Iodobenzylguanidine↗

PubMed2002

Evaluation of four postprocessing methods for determination of cerebral blood volume and mean transit time by dynamic susceptibility contrast imaging.

Four different postprocessing methods to determine cerebral blood volume (CBV) and contrast agent mean transit time (MTT) by dynamic susceptibility contrast (DSC) MRI were compared. CBV was determined by two different methods that integrate tracer concentration-time curves numerically and by two other methods that take recirculation into account. For the two methods that use numerical integration, one method cuts the integration after the first pass while the other method integrates over the whole time series. For the two methods that account for recirculation, one method uses a gamma-variate fit, whereas the other method utilizes tissue impulse response. All four methods determine MTT as the ratio of CBV and cerebral blood flow (CBF). In each case, CBF was obtained as the height of the impulse response obtained by deconvolving the tissue concentration-time curves with a noninvasively determined arterial input function. Monte Carlo simulations were performed to determine the reliability of the methods and the validity of the simulations was supported by observation of similar trends in 13 acute stroke patients. The method of determining CBV and subsequently MTT was found to affect the measured value especially in areas where MTT is prolonged, but had no apparent effect on the visually determined hypoperfusion volumes.

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