Dynamic susceptibility contrast MRI may contribute in prediction of stereotactic radiosurgery outcome in brain metastases.

Background: Following stereotactic radiosurgery (SRS), predicting treatment response is not possible at an early stage using structural imaging alone. Hence, the current study aims at investigating whether dynamic susceptibility contrast (DSC)-MRI estimated prior to SRS can provide predictive biomarkers in response to SRS treatment and characterize vascular characteristics of pseudo-progression. Methods: In this retrospective study, perfusion-weighted DSC-MRI image data acquired with a temporal resolution of 1.45 seconds were collected from 41 patients suffering from brain metastases. Outcome was defined based on lesion volume changes in time (determined on structural images) or death. Motion correction and manual lesion delineation were performed prior to semi-automated, voxel-wise perfusion analysis. Statistical testing was performed using linear regression and a significance threshold at P = .05. Age, sex, primary cancers (pulmonary cancer and melanoma), lesion volume, and dichotomized survival time were added as covariates in the linear regression models (ANOVA). Results: Relative cerebral blood volume (rCBV) and relative cerebral blood flow (rCBF) were found to be significantly lower prior to SRS treatment in patients with increasing lesion volume or early death post-SRS (P ≤ .01). Conclusion: Unfavorable treatment outcome may be linked to low perfusion prior to SRS. Pseudo-progression may be preceded by a transient rCBF increase post-SRS. However, results should be verified in different or larger patient material.

Impaired cerebrovascular reactivity may predict delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage.

INTRODUCTION: Delayed cerebral ischemia (DCI) is a major cause of disability and death after aneurysmal subarachnoid hemorrhage. The literature suggests that impaired cerebrovascular reactivity (CVR) may be a predictor for DCI; still no CVR based prediction model has been developed. Increased knowledge about possible predictors of DCI can improve patient management in high-risk patients and allow for shorter hospital stay in low-risk patients. METHOD: CVR was examined in 42 patients with aneurysmal subarachnoid hemorrhage and 37 patients treated for unruptured intracranial aneurysm, using acetazolamide test with transcranial Doppler monitoring of blood flow velocities. Patients were followed for development of DCI, separated into clinical deterioration and radiographic infarction. RESULTS: For all patients, regardless of aneurysm rupture status, CVR was on average 5.5 percentage points lower on the ipsilateral side of aneurysm treatment. Patients with clinical deterioration due to DCI had lower CVR than patients without DCI, and the difference was larger on the contralateral side (33.9% vs. 49.2%). Two prediction models were constructed for clinical deterioration due to DCI. The area under the receiver operating characteristic curve was 0.82 in the model using established predictors, and 0.86 in the model that also included CVR. CONCLUSION: Our findings support the hypothesis that impaired CVR may be an independent predictor of clinical deterioration due to DCI, and may assist in identifying patients at risk after aneurysmal subarachnoid hemorrhage. Ipsilateral CVR reduction occurs in all patients after aneurysm treatment, regardless of DCI development, thus highlighting the need to evaluate ipsi- and contralateral CVR separately.

A stress-related explanation to the increased blood pressure and its course following ischemic stroke.

BACKGROUND: A hypertensive response after ischemic stroke is frequent, yet its pathophysiology is unknown. Mechanisms related to local ischemic damage, major vascular occlusion, and psychological stress due to acute illness have been proposed. We assessed the natural course of blood pressure (BP) within the first 24 h in groups of ischemic stroke patients with different characteristics. We hypothesized that a consistent BP reduction, regardless of stroke location, time window from debut to admission and presence of persistent vascular occlusion, would favor a stress-related mechanism as an important cause of the hypertensive response after ischemic stroke. METHODS: Ischemic stroke patients (n=1067) were prospectively registered, and BP was measured on admission and <3 h, 3-6 h, 6-12 h and 12-24 h after admission. Patients were categorized according to the location of diffusion-weighted imaging (DWI) lesions (cortical, large subcortical, mixed cortico-subcortical, lacunar, cerebellar, brain stem or multiple), time window (admitted within or after 6 h of symptom onset) and presence of persistent proximal middle cerebral artery (MCA) occlusion versus normal findings on magnetic resonance angiography (MRA) at 24 h. RESULTS: A reduction in systolic BP and diastolic BP from baseline to 12-24 h was found across all DWI locations except for diastolic BP in cerebellar (P=0.072) lesions. Apart from diastolic BP in patients with normal MRA findings at 24 h (P=0.060), a significant fall in systolic BP and diastolic BP at 12-24 h was registered, irrespective of whether patients were admitted within 6 h or after 6 h of stroke onset or had persistent MCA occlusion versus normal MRA findings. CONCLUSION: We found a relatively consistent decline in BP within 24 h after admission across different stroke locations in patients admitted within or after 6 h of stroke onset and in patients with persistent MCA occlusion. Our findings suggest that a systemic factor such as psychological stress may be an important contributor to the frequently elevated BP on admission in patients with ischemic stroke.

[A 4-year-old girl with diarrhoea, paresis and mutism]. / En fire år gammel jente med diaré, kraftsvikt og mutisme.

BACKGROUND Rotavirus is a common cause of gastroenteritis in children. Neurological manifestations associated with rotavirus infections are well described and range from benign afebrile convulsions to lethal encephalopathy or encephalitis.CASE PRESENTATION We present an uncommon neurological manifestation in a Caucasian child in the course of a rotavirus infection. A 4-year old girl presented with mutism, hypotonia and reduced consciousness. Magnetic resonance imaging revealed diffusion abnormalities in the splenium corpus callosum and bilaterally in the nuclei dentate in the cerebellum. She was diagnosed with rotavirus cerebellitis.INTERPRETATION Her clinical symptoms and the magnetic resonance imaging abnormalities were uncommon and previously described in only a few Caucasian children. The outcome has varied, and some children have shown long term neurological sequela. Treatment with immunoglobulins and corticosteroids has been used in similar cases, but there is no established treatment for this condition.

A Randomized Controlled Trial To Assess and Compare the Outcomes of Two-core Prostate Biopsy Guided by Fused Magnetic Resonance and Transrectal Ultrasound Images and Traditional 12-core Systematic Biopsy.

BACKGROUND: Prostate biopsy guided by computer-assisted fusion of magnetic resonance imaging (MRI) and transrectal ultrasound (TRUS) images (MRI group) has not yet been compared with 12-core random biopsy (RB; control group) in a randomized controlled trial (RCT). OBJECTIVE: To compare the rate of detection of clinically significant prostate cancer (csPCa) between the two groups. DESIGN, SETTING, AND PARTICIPANTS: This RCT included 175 biopsy-naïve patients with suspicion for prostate cancer, randomized to an MRI group (n=86) and a control group (n=89) between September 2011 and June 2013. INTERVENTION: In the MRI group, two-core targeted biopsy (TB) guided by computer-assisted fusion of MRI/TRUS images of MRI-suspicious lesions was followed by 12-core RB. In the control group, both two-core TB for abnormal digital rectal examination (DRE) and/or TRUS-suspicious lesions and 12-core RB were performed. In patients with normal MRI or DRE/TRUS, only 12-core RB was performed. OUTCOMES MEASUREMENTS AND STATISTICAL ANALYSIS: The detection rates for any cancer and csPCa were compared between the two groups and between TB and RB. RESULTS AND LIMITATIONS: Detection rates for any cancer (MRI group 51/86, 59%; control group 48/89, 54%; p=0.4) and csPCa (38/86, 44% vs 44/89, 49%; p=0.5) did not significantly differ between the groups. Detection of csPCa was comparable between two-core MRI/TRUS-TB (33/86, 38%) and 12-core RB in the control group (44/89, 49%; p=0.2). In a subset analysis of patients with normal DRE, csPCa detection was similar between two-core MRI/TRUS-TB (14/66, 21%) and 12-core RB in the control group (15/60, 25%; p=0.7). Among biopsy-proven csPCas in MRI group, 87% (33/38) were detected by MRI/TRUS-TB. The definition of csPCa was only based on biopsy outcomes. CONCLUSION: Overall csPCa detection was similar between the MRI and control groups. Two-core MRI/TRUS-TB was comparable to 12-core RB for csPCa detection. PATIENT SUMMARY: Our randomized controlled trial revealed a similar rate of prostate cancer detection between targeted biopsy guided by magnetic resonance imaging (MRI) and transrectal ultrasound (TRUS) and 12-core random biopsy. The traditional 12-core random biopsy may be replaced by two-core MRI/TRUS targeted biopsy for detection of clinically significant prostate cancer.

Diffusion-weighted lesions in stroke patients with transient symptoms--where are they located?

BACKGROUND: MR diffusion-weighted imaging (DWI) has revolutionized neuroimaging and contributed to a tissue-based redefinition of transient ischemic attack (TIA). Stroke patients with DWI lesions may have neurological symptoms that resolve completely within 24 h, suggesting successful vessel recanalization. Prior studies of stroke patients with transient symptoms have not found any predilection for DWI lesions in any specific territory. Other studies have, however, reported an association between higher brain dysfunction and presence of DWI lesions in patients with transient ischemic symptoms, suggesting a high rate of cortical affection in these patients. We sought to see whether DWI location in stroke patients with transient symptoms <24 h differed from those with persistent symptoms ≥ 24 h. We hypothesized an association between transient symptoms <24 h and cortical DWI lesion localization due to a possible higher rate of vessel recanalization in patients with transient symptoms causing distal cortical infarctions. METHODS: Ischemic stroke patients examined with DWI and admitted within 24 h after symptom onset between February 2006 and November 2013 were prospectively registered in a database (The Bergen NORSTROKE Registry). Based on neurological examination 24 h after admission, patients were classified as having either transient symptoms <24 h (DWI <24) or persistent symptoms ≥ 24 h (DWI ≥ 24). DWI lesions were classified into different groups depending on lesion location: cortical lesions, confined to the supratentorial cortex; large subcortical lesions, located in the hemispheric white matter, basal ganglia, internal capsule, thalamus or corona radiate with a diameter ≥ 15 mm; lacunar lesions, located in the same territory as large subcortical lesions with a diameter <15 mm; mixed cortical-subcortical lesions, located in both supratentorial cortex and subcortex; cerebellar lesions, confined to the cerebellum; brain stem lesions, confined to the brain stem; multiple locations, located in more than one of the above defined areas. RESULTS: A total of 142 ischemic stroke patients had DWI <24 and 830 DWI ≥ 24. Cortical DWI location was more frequent in patients with DWI <24 (54.2% vs. 29.5%, p < 0.001), while proportions of mixed cortical-subcortical lesions (13.4% vs. 26.5%, p = 0.001) and lesions with multiple locations (5.6% vs. 11.1%, p = 0.048) were less frequent as compared to DWI ≥ 24. Cortical DWI location was independently associated with DWI <24 when adjusted for confounders in multiple regression analyses (OR 1.89, 95% CI 1.28-2.81, p = 0.001). CONCLUSION: Cortical DWI location was independently associated with transient stroke symptoms <24 h. This may be explained by vessel recanalization, resulting in upstream transportation of remaining particles and distal cortical lesions.

A dark side of subcortical diffusion-weighted lesions? Characteristics, cause, and outcome in large subcortical infarction: the Bergen Norwegian stroke cooperation study.

BACKGROUND AND PURPOSE: Diffusion-weighted imaging (DWI) is highly accurate in identifying and locating ischemic stroke injury. Few studies using DWI have investigated large subcortical infarctions (LSIs). We aimed to study clinical characteristics, cause, and outcome in patients with ischemic stroke with LSI diagnosed on DWI and compare these with those who had lacunar DWI lesions or DWI lesions located elsewhere. METHODS: Patients with stroke admitted between February 2006 and July 2013 were prospectively registered in a stroke database and examined with DWI. Patients with DWI lesions classified as LSI (subcortical, ≥15 mm) were compared with those with lacunar lesions (subcortical, <15 mm, lacunar infarction [LI]), cortical lesions (cortical infarction [CI]), or no LSI, which included LI, CI, mixed cortical-subcortical, cerebellar, brain stem, and combined lesion locations. RESULTS: A total of 1886 patients with ischemic stroke were included, of which 128 patients (6.8%) had LSI, 317 (16.8%) LI, and 544 (28.8%) CI. The no LSI group included 1758 patients. Occlusive pathology in the proximal middle cerebral artery was more frequent in patients with acute stroke with LSI. Lacunar syndrome was associated with LSI when compared with CI and no LSI. Unknown cause was frequent in the LSI group (60.4%) and independently associated with LSI in the LSI versus LI (P<0.001), LSI versus CI (P=0.002), and LSI versus no LSI population (P<0.001). LSI was independently associated with unfavorable outcome, whether compared with LI (P=0.002), CI (P<0.001), or no LSI (P=0.002). CONCLUSIONS: LSI is associated with distinct clinical characteristics, unknown cause, and unfavorable outcome, which separates this stroke entity from patients with lacunar subcortical DWI lesions or DWI lesions located elsewhere.

Spinous process osteotomy to facilitate the access to the spinal canal when decompressing the spinal canal in patients with lumbar spinal stenosis.

STUDY DESIGN: Retrospective study. PURPOSE: The main purpose of this study was to investigate the union-rate of the spinous process after performing a spinous process osteotomy and whether union affects the clinical results after surgery. OVERVIEW OF LITERATURE: In the present study, spinous process osteotomy was used to facilitate access to the spinal canal when performing a decompressive procedure for lumbar spinal stenosis. The aim of this study was to evaluate the union rate of the spinous process and its effect on the clinical results of the procedure. METHODS: All patients were included in the study that underwent a decompressive procedure through spinous process osteotomy be between January 1, 2007 and December 31, 2007. Operation protocols were reviewed. A computed tomography (CT) scan was performed to evaluate the union of the osteotomies of the spinous process. According to the CT-scans, patients were divided into three groups: "complete-union," "partial-union," and "non-union." Patients reported their clinical results through a self-administered questionnaire. RESULTS: The mean period of follow up was 21.6 months (range, 16-28 months). A total of 44% of the performed osteotomies were considered as united. Ten patients (18%) were classified as "complete-union," 30 patients (55%) as "partial-union," and 15 patients (27%) as "non-union." The "complete-union" group showed better clinical results and scored significantly better in the Oswestry Disability Index and EQ-5D. However, no statistical difference was found in the pain-scores. There were no differences between the "partial-union" group and the "no-union" group. CONCLUSIONS: We found a radiologic union for 60 out of 135 (44%) spinous process osteotomies.

Laminarthrectomy as a surgical approach for decompressing the spinal canal: assessment of preoperative versus postoperative dural sac cross-sectional areal (DSCSA).

INTRODUCTION: Surgery for lumbar spinal stenosis (LSS) is today the most frequently performed procedure in the adult lumbar spine. Long-term benefit of surgery for LSS is well documented both in randomized and in non-randomized trials. In this paper, we present the results from laminarthrectomy as an alternative surgical approach, which have theoretical advantages over other approaches. In this study, we wanted to study the clinical and radiological results of laminarthrectomy. Dural sac cross-sectional areal (DSCSA) is an objective method to quantify the degree of central stenosis in the spinal canal, and was used to measure whether we were able to achieve an adequate decompression of the spinal canal with laminarthrectomy as a surgical approach. MATERIALS AND METHODS: All patients operated on with this approach consecutively in the period 1 January 2008 to 31 March 2009 were included in the study. All perioperative complications were noted. Clinical results were measured by means of a questionnaire. The patients that agreed to attend the study had an MRI taken of the operated level. DSCSA before and after surgery of the actual level were measured by three observers. We then performed a correlation test between increase of area and clinical results. We also tested for inter- and intra-observer reability. RESULTS: Fifty-six laminarthrectomy were performed. There were 17% complications, none of them were life-threatening or disabling. 46 patients attended the study and answered the questionnaire. Thirty-four patients (83%) reported clinical improvement, whereas six (13%) patients reported no improvement, and two (4%) patients reported that they were worse. Mean ODI was 23.0. Mean EQ-5D was 0.77. Mean VAS-score for back-pain was 3.1 and mean VAS-score for leg-pain was 2.8. Mean DSCSA were measured to 80 mm(2) before surgery and 161 mm(2) after surgery. That gave an increase of DSCSA of 81 mm(2) (101%). We found a significant positive correlation between increase of area and clinical results. We also found consistent inter- and intra-observer reability. DISCUSSION: In this study, the clinical results of laminarthrectomy were good, and comparable with other reports for LSS. The rates of complications are also comparable with other reports in spinal surgery. A significant increase in the spinal canal diameter was achieved. Within the limitations a retrospective study gives, we conclude that laminarthrectomy seems to be a safe and effective surgical approach for significant decompressing the adult central spinal canal, and measurement of DSCSA, before and after surgery seems to be a good way to quantify the degree of decompression.

Pneumocephalus, a rare complication of diving.

BACKGROUND: Pneumocephalus is a recognized complication from head and facial traumas, sinus surgery and as a complication from otitis media acuta. Only a few cases of pneumocephalus related to diving have been reported. HISTORY: We report an occupational diver who suffered spontaneous subarachnoidal pneumocephalus related to a dive to 20 meters. At a depth of 17 msw he suffered from sudden onset of headache, dizziness, nausea and feeling of disorientation. He had no recognized risk factors such as documented facial fractures, rapid ascent or blocked sinuses. CT showed air in the subarachnoidal space. Otoneurological tests revealed pathological smooth pursuit tracking eye movements and substantial imbalance indicating a central neurological injury. CT and MRI showed a bony defect in the sphenoid sinus covered only by arachnoidea. This was probably the communicative fistula for the entrance of air. On follow-up examination one year later he still had central nervous symptoms and signs, as well as symptoms of post-traumatic stress disorder (PTSD.) He was not able to do any work and was declared unfit for further diving. We chose not to treat him with hyperbaric oxygen (HBO2) in the acute state because we thought HBO2 might have increased the amount of intracranial air. CONCLUSION: Pneumocephalus is a rare, but serious complication of diving. The condition should be suspected in a diver with increasing headache or other central nervous disturbancies during ascent. The treatment of pneumocephalus in divers is a matter of debate.

Cerebral diffusion and perfusion deficits in North Sea divers.

BACKGROUND: Diving is associated with a risk of cerebral decompression illness, and the prevalence of neurological symptoms is higher in divers compared with control groups. Microvascular dysfunction due to gas microembolism and exposure to hyperoxia are possible mechanisms, which may result in cerebral diffusion and perfusion deficits. PURPOSE: To investigate if possible functional derangements of the microvasculature and microstructure would be more prevalent among symptomatic divers. MATERIAL AND METHODS: Magnetic resonance imaging (MRI) was performed in 91 former divers and 45 controls. Individual parametric images of apparent diffusion coefficient (ADC), cerebral blood flow (CBF), cerebral blood volume (CBV), and mean transit time (MTT) were generated on the basis of diffusion- and perfusion-weighted imaging. To identify regions with statistically significant differences between groups (P < 0.05, corrected for false discovery rate), voxel-wise ANCOVA analysis was performed for each of the four parametric images. RESULTS: Significant regional group differences were found in all four parametric comparisons. Gross regional ADC differences were seen throughout the brain, including large frontal and temporal white-matter regions, the hippocampus, and parts of the cerebellum. Differences in the perfusion maps were localized in fewer and smaller clusters, including parts of the cerebellum, the putamen, and the anterior watershed regions. CONCLUSION: Regional functional abnormalities as measured by diffusion- and perfusion-weighted imaging were identified in the divers, and there was a partial co-localization of the regions identified in the perfusion and the diffusion images. The findings may explain some of the long-term clinical symptoms reported among professional divers.

Localized cerebral energy failure in DNA polymerase gamma-associated encephalopathy syndromes.

Mutations in the catalytic subunit of the mitochondrial DNA-polymerase gamma cause a wide spectrum of clinical disease ranging from infantile hepato-encephalopathy to juvenile/adult-onset spinocerebellar ataxia and late onset progressive external ophthalmoplegia. Several of these syndromes are associated with an encephalopathy that characteristically shows episodes of rapid neurological deterioration and the development of acute cerebral lesions. The purpose of this study was to investigate the nature, distribution and natural evolution of central nervous system lesions in polymerase gamma associated encephalopathy focusing particularly on lesions identified by magnetic resonance imaging. We compared radiological, electrophysiological and pathological findings where available to study potential mechanisms underlying the episodes of exacerbation and acute cerebral lesions. We studied a total of 112 magnetic resonance tomographies and 11 computed tomographies in 32 patients with polymerase gamma-encephalopathy, including multiple serial examinations performed during both the chronic and acute phases of the disease and, in several cases, magnetic resonance spectroscopy and serial diffusion weighted studies. Data from imaging, electroencephalography and post-mortem examination were compared in order to study the underlying disease process. Our findings show that magnetic resonance imaging in polymerase gamma-related encephalopathies has high sensitivity and can identify patterns that are specific for individual syndromes. One form of chronic polymerase gamma-encephalopathy, that is associated with the c.1399G > A and c.2243G > C mutations, is characterized by progressive cerebral and cerebellar atrophy and focal lesions of the thalamus, deep cerebellar structures and medulla oblongata. Acute encephalopathies, both infantile and later onset, show similar pictures with cortical stroke-like lesions occurring during episodes of exacerbation. These lesions can occur both with and without electroencephalographic evidence of concurrent epileptic activity, and have diffusion, spectroscopic and histological profiles strongly suggestive of neuronal energy failure. We suggest therefore that both infantile and later onset polymerase gamma related encephalopathies are part of a continuum.

Voxel-specific brain arterial input functions from dynamic susceptibility contrast MRI and blind deconvolution in a group of healthy males.

BACKGROUND: Arterial input functions may differ between brain regions due to delay and dispersion effects in the vascular supply network. Unless corrected for, these differences may degrade quantitative estimations of cerebral blood flow in dynamic susceptibility contrast magnetic resonance perfusion imaging (DSC-MRI). PURPOSE: To investigate in a healthy population (n=44) the properties of voxel-specific arterial input functions that were obtained using a recently published blind estimation approach. MATERIAL AND METHODS: The voxel-specific arterial input functions were qualitatively and quantitatively assessed, through visual inspection or by comparing time-to-peak (delays) and peak amplitude (dispersion) values between eight regions of the brain. Furthermore, they were compared to arterial input functions selected manually in the middle cerebral artery (MCA), where normally no delay or dispersion of the contrast agent was expected. RESULTS: The estimated voxel-specific arterial input functions varied between brain regions. Differences in delays and dispersion were larger within one brain region among all participants than between regions in one participant. A good correlation was typically found between the estimated voxel-specific arterial input functions and the manually selected arterial input functions in the MCA region. CONCLUSION: Given knowledge of neurovascular anatomy, the current blind approach seemingly produced reasonable estimates of voxel-specific arterial input functions. In addition to potentially reducing quantification errors in DSC-MRI, these user-independent voxel-specific arterial input functions could be useful for visualizing abnormal blood supply patterns in patients.

Clinical presentation and diffusion weighted MRI of acute cerebral infarction. The Bergen Stroke Study.

BACKGROUND: No large study has compared the yield of diffusion-weighted imaging (DWI) with clinical examination in order to differentiate lacunar stroke from other stroke subtypes. This differentiation is important for guiding further investigations and treatment. METHODS: Consecutive patients admitted with cerebral infarction were classified according to the Oxfordshire Community Stroke Project scale. Based on DWI and CT stroke was classified as lacunar (LI) and non-lacunar (NLI). Acute ischemic lesion <1.5 cm and located in subcortex or in brainstem were classified as LI. All other infarctions were classified as NLI. RESULTS: DWI was performed in 419 (69%) patients. Among patients with lacunar syndrome (LACS) 45 (40.5%) had NLI on DWI. All patients with total anterior syndrome (TACS) and 144 (88.3%) with partial anterior syndrome (PACS) had NLI on DWI. CONCLUSION: DWI is important among patients presenting with clinical symptoms suggestive of lacunar syndrome to differentiate between LI and NLI. On the other hand, there is good correspondence between TACS or PACS and NLI on DWI.

[Decompressive craniectomy in acute encephalitis]. / Dekomprimerende kraniektomi ved akutt encefalitt.

We report a patient with acute encephalitis of unknown causation who underwent hemicraniectomy because of threatening herniation. The patient recovered uneventfully and three weeks later, findings on neurological examination were normal. Hemicraniectomy should be considered in all patients with encephalitis and threatening herniation.

Magnetic resonance brain perfusion imaging with voxel-specific arterial input functions.

PURPOSE: To propose an automatic method for estimating voxel-specific arterial input functions (AIFs) in dynamic contrast brain perfusion imaging. MATERIALS AND METHODS: Voxel-specific AIFs were estimated blindly using the theory of homomorphic transformations and complex cepstrum analysis. Wiener filtering was used in the subsequent deconvolution. The method was verified using simulated data and evaluated in 10 healthy adults. RESULTS: Computer simulations accurately estimated differently shaped, normalized AIFs. Simple Wiener filtering resulted in underestimation of flow values. Preliminary in vivo results showed comparable cerebral flow value ratios between gray matter (GM) and white matter (WM) when using blindly estimated voxel-specific AIFs or a single manually selected AIF. Significant differences (P < or = 0.0125) in mean transit time (MTT) and time-to-peak (TTP) in GM compared to WM was seen with the new method. CONCLUSION: Initial results suggest that the proposed method can replace the tedious and difficult task of manually selecting an AIF, while simultaneously providing better differentiation between time-dependent hemodynamic parameters.