Abstract: Perfusion is a fundamental biological function that refers to the delivery of oxygen and nutrients to tissue by means of blood flow. Perfusion MRI is sensitive to microvasculature and has been applied in a wide variety of clinical applications, including the classification of tumors, identification of stroke regions, and characterization of other diseases. Perfusion MRI techniques are classified with or without using an exogenous contrast agent. Bolus methods, with injections of a contrast agent, provide better sensitivity with higher spatial resolution, and are therefore more widely used in clinical applications. However, arterial spin-labeling methods provide a unique opportunity to measure cerebral blood flow without requiring an exogenous contrast agent and have better accuracy for quantification. Importantly, MRI-based perfusion measurements are minimally invasive overall, and do not use any radiation and radioisotopes. In this review, we describe the principles and techniques of perfusion MRI. This review summarizes comprehensive updated knowledge on the physical principles and techniques of perfusion MRI.

Abstract: Purpose To evaluate the feasibility of intravoxel incoherent motion (IVIM) perfusion measurements in the brain with currently available imaging systems. Materials and Methods We acquired high in-plane resolution (1.2 × 1.2 mm) diffusion-weighted images with 16 different values of b ranging from 0 to 900 s/mm, in three orthogonal directions, on 3T systems with a 32-multichannel receiver head coil. IVIM perfusion maps were extracted by fitting a double exponential model of signal amplitude decay. Regions of interest were drawn in pathological and control regions, where IVIM perfusion parameters were compared to the corresponding dynamic susceptibility contrast (DSC) parameters. Results Hyperperfusion was found in the nonnecrotic or cystic part of two histologically proven glioblastoma multiforme and in two histologically proven glioma WHO grade III, as well as in a brain metastasis of lung adenocarcinoma, in a large meningioma, and in a case of ictal hyperperfusion. A monoexponential decay was found in a territory of acute ischemia, as well as in the necrotic part of a glioblastoma. The IVIM perfusion fraction f correlated well with DSC CBV. Conclusion Our initial report suggests that high-resolution brain perfusion imaging is feasible with IVIM in the current clinical setting. J. Magn. Reson. Imaging 2014;39:624-632. © 2013 Wiley Periodicals, Inc.

Abstract: CT perfusion imaging is a promising technique for diagnosing primary or metastatic tumors, for assessing the efficacy of systemic or local tumor therapy, for predicting early response to anticancer treatments, and for monitoring tumor recurrence after therapy.

Abstract: Computed tomographic (CT) coronary angiography is a well-established, noninvasive imaging modality for detection of coronary stenosis, but it has limited accuracy in demonstrating whether a coronary stenosis is hemodynamically significant. An additional functional test is often required because both anatomic and functional information is needed for guiding patient care. Recent developments in CT technology allow CT evaluation of myocardial perfusion during vasodilator stress, thereby providing information about myocardial ischemia. Investigators in several single-center studies have established the feasibility of performing stress myocardial perfusion CT imaging in small groups of patients and have shown that stress myocardial perfusion CT in combination with CT coronary angiography improved the diagnostic accuracy in comparison with CT coronary angiography alone. However, CT perfusion acquisition protocols must be optimized in terms of acquisition and reconstruction parameters, contrast material protocol injections, and radiation dose. Further research is needed to establish the clinical usefulness of this novel technique. The purpose of this review is to (a) provide an overview of the physiology of coronary circulation and myocardial perfusion; (b) describe the technical prerequisites, challenges, and mathematic modeling related to CT perfusion imaging; (c) note recent advances in CT scanners and CT perfusion protocols; and (d) discuss the interpretation of CT perfusion images. Finally, a review and summary of the current literature are provided, and future directions for research are discussed.

Abstract: Background and Purpose—If magnetic resonance imaging (MRI) is to compete with computed tomography for evaluation of patients with acute ischemic stroke, there is a need for further improvements in acquisition speed. Methods—Inclusion criteria for this prospective, single institutional study were symptoms of acute ischemic stroke within 24 hours onset, National Institutes of Health Stroke Scale ≥3, and absence of MRI contraindications. A combination of echo-planar imaging (EPI) and a parallel acquisition technique were used on a 3T magnetic resonance (MR) scanner to accelerate the acquisition time. Image analysis was performed independently by 2 neuroradiologists. Results—A total of 62 patients met inclusion criteria. A repeat MRI scan was performed in 22 patients resulting in a total of 84 MRIs available for analysis. Diagnostic image quality was achieved in 100% of diffusion-weighted imaging, 100% EPI-fluid attenuation inversion recovery imaging, 98% EPI-gradient recalled echo, 90% neck MR angiography an...

Abstract: In this prospective, multicenter study, myocardial CT perfusion imaging demonstrated higher overall diagnostic performance, as demonstrated with the area under the receiver operating characteristic curve, compared with SPECT for the diagnosis of anatomic stenosis of at least 50%.

Abstract: To date, the most frequently used Parkinson's disease (PD) biomarkers are the brain imaging measures of dopaminergic dysfunction using positron emission tomography and single photon emission computed tomography. However, major advances have occurred in the development of magnetic resonance imaging (MRI) biomarkers for PD in the past decade. Although conventional structural imaging remains normal in PD, advanced techniques have shown changes in the substantia nigra and the cortex. The most well-developed MRI markers in PD include diffusion imaging and iron load using T2/T2* relaxometry techniques. Other quantitative biomarkers such as susceptibility-weighted imaging for iron load, magnetization transfer and ultra-high-field MRI have shown great potential. More sophisticated techniques such as tractography and resting state functional connectivity give access to anatomical and functional connectivity changes in the brain, respectively. Brain perfusion can be assessed using non-contrast-agent techniques such as arterial spin labelling and spectroscopy gives access to metabolites concentrations. However, to date these techniques are not yet fully validated and standardized quantitative metrics for PD are still lacking. This review presents an overview of new structural, perfusion, metabolic and anatomo-functional connectivity biomarkers, their use in PD and their potential applications to improve the clinical diagnosis of Parkinsonian syndromes and the quality of clinical trials.

Abstract: Background and Purpose—Vertebral artery hypoplasia (VAH) is supposed to be a risk factor for posterior circulation ischemia (PCI), particularly in the territory of the posterior inferior cerebellar artery (PICA). The aim of our study was to determine whether VAH impedes perfusion in the dependent PICA territory even in the absence of manifest PCI. Methods—VA diameter was retrospectively measured in 934 consecutive patients who underwent whole-brain multimodal computed tomography because of suspected stroke. VAH was defined by a diameter of ≤2 mm and an asymmetry ratio of ≤1:1.7 of both VAs. We performed blinded computed tomography perfusion reading in patients with VAH without PCI (MRI-confirmed) and in control patients (ratio 1:2) with normal VAs. Four different perfusion maps were evaluated for a relative hypoperfusion in the PICA territory. Results—VAH was found in 146 of 934 patients (15.6%). It was more frequent on the right side (66.1%). Of 146 patients, 59 without PCI qualified for computed tomogra...

Abstract: Longitudinal PET-MRI study on the dynamics of β-amyloid deposition and regional cerebral blood flow in the Alzheimer's disease mouse brain.

Abstract: Delayed cerebral ischemia (DCI) is at presentation a diagnosis per exclusionem, and can only be confirmed with follow-up imaging. For treatment of DCI a diagnostic tool is needed. We performed a systematic review to evaluate the value of CT perfusion (CTP) in the prediction and diagnosis of DCI. We searched PubMed, Embase, and Cochrane databases to identify studies on the relationship between CTP and DCI. Eleven studies totaling 570 patients were included. On admission, cerebral blood flow (CBF), cerebral blood volume (CBV), mean transit time (MTT), and time-to-peak (TTP) did not differ between patients who did and did not develop DCI. In the DCI time-window (4 to 14 days after subarachnoid hemorrhage (SAH)), DCI was associated with a decreased CBF (pooled mean difference −11.9 mL/100 g per minute (95% confidence interval (CI): −15.2 to −8.6)) and an increased MTT (pooled mean difference 1.5 seconds (0.9–2.2)). Cerebral blood volume did not differ and TTP was rarely reported. Perfusion thresholds reported in studies were comparable, although the corresponding test characteristics were moderate and differed between studies. We conclude that CTP can be used in the diagnosis but not in the prediction of DCI. A need exists to standardize the method for measuring perfusion with CTP after SAH, and optimize and validate perfusion thresholds.

Abstract: Objective The aim of this pilot study was to assess peripheral blood perfusion (PBP) by a new technique, the laser speckle contrast analysis (LASCA), in systemic sclerosis (SSc) patients showing different patterns of nailfold microangiopathy. Correlations between LASCA and single laser Doppler flowmetry (LDF) analysis were also checked. Methods Sixty-one SSc patients and 61 healthy subjects were enrolled. PBP was evaluated using LASCA and LDF. Scleroderma patterns and microangiopathy evolution score (MES) were assessed by nailfold videocapillaroscopy (NVC). Results As detected by LASCA and LDF, PBP was lower in SSc patients than in healthy subjects (p Conclusions LASCA detected lower PBP in SSc patients than in healthy subjects, and for the first time, LASCA perfusion values were found correlated with progression of NVC patterns of microangiopathy.

Abstract: Background Microvascular dysfunction in HCM has been associated with adverse clinical outcomes. Advances in quantitative cardiovascular magnetic resonance (CMR) perfusion imaging now allow myocardial blood flow to be quantified at the pixel level. We applied these techniques to investigate the spectrum of microvascular dysfunction in hypertrophic cardiomyopathy (HCM) and to explore its relationship with fibrosis and wall thickness.

Abstract: Background and Purpose—Arterial spin labeling (ASL) is a perfusion magnetic resonance imaging (MRI) technique that does not require contrast administration and thus may be more practical in hyperac...

Abstract: Hypertension may increase risk for dementia possibly because of its association with decreased cortical thickness. Disturbed cerebral autoregulation is one plausible mechanism by which hypertension impacts the cerebral structure, but the associations among hypertension, brain perfusion, and cortical thickness are poorly understood. The current sample consisted of 58 older adults with varying levels of vascular disease. Diagnostic history of hypertension and antihypertensive medication status was ascertained through self-report, and when available, confirmed by medical record review. All participants underwent arterial spin labeling and T1-weighted magnetic resonance imaging to quantify total and regional cortical perfusion and thickness. Analysis of covariance adjusting for medical variables showed that participants with hypertension exhibited reduced temporal and occipital brain perfusion and total and regional cortical thickness relative to those without hypertension. The effects of hypertension on total brain perfusion remained unchanged even after adjustment for age, although no such pattern emerged for cortical thickness. Decreased total brain perfusion predicted reduced thickness of the total brain and of the frontal, temporal, and parietal lobe cortices. Antihypertensive treatment was not associated with total cerebral perfusion or cortical thickness. This study provides initial evidence for the adverse effects of a diagnostic history of hypertension on brain hypoperfusion and reduced cortical thickness. Longitudinal studies are needed to investigate the role of hypertension and its interaction with other contributing factors (eg, age) in the manifestation of cerebral hypoperfusion and reduced cortical thickness.

Abstract: The foundation of modern therapy for ischaemic stroke involves reperfusion of the ischaemic penumbra and salvage of threatened but potentially viable brain tissue. Work on imaging of the penumbra and clinical trials using penumbral evaluation or selection have been a major focus of our collaborative work over several decades. We review the original description of the ischaemic penumbra, its measurement using a variety of imaging techniques, the duration of the penumbra and its potential salvage up to 48 h after stroke onset. The penumbra can now be accurately measured using automated thresholded techniques in real time with MRI or CT perfusion (CTP). Particular advances include more precise definitions of mismatch with validation of the measures for the ischaemic core and exclusion of benign oligaemia. While there has been greater trial experience with MRI perfusion/diffusion mismatch, CTP mismatch using a similar thresholded perfusion metric (Tmax 6 s) and relative blood flow (around 31%) to estimate the ischaemic core is generally more available and practicable in our experience. We review the completed clinical trials, which generally demonstrate the clinical benefits of acute reperfusion in penumbral patients, provided that large ischaemic cores are excluded. Our EPITHET trial was the first randomized controlled trial of tissue plasminogen activator (tPA) versus placebo at delayed times to test the concept of penumbral selection. We showed that in patients with a penumbra receiving thrombolysis, there was substantially increased reperfusion. Major reperfusion times were associated with reduced growth of the ischaemic core and improved clinical outcomes. Our current trial programme involves the application of penumbral imaging to attempt to extend the time window for intravenous tPA and treat wake-up strokes, to test the benefits of endovascular therapy in patients who have already received tPA but still have both substantial penumbra and an occluded vessel, and, finally, to use penumbral imaging to define a responder population in a phase III trial testing intravenous tenecteplase versus tPA within the current 4.5-hour time window. We believe that confirmation of these trial hypotheses will substantiate the role of multimodal imaging of the penumbra as a routine part of acute stroke management.

Abstract: Because of its noninvasive nature and provision of quantitative measures of a wide variety of physiologic parameters, functional magnetic resonance imaging (MRI) shows great potential for research and clinical applications. Over the past decade, application of functional MRI extended beyond detection of cerebral activity, and techniques for abdominal functional MRI evolved. Assessment of renal perfusion, glomerular filtration, interstitial diffusion, and parenchymal oxygenation turned this modality into an essential research and potentially diagnostic tool. Variations in many renal physiologic markers can be detected using functional MRI before morphologic changes become evident in anatomic magnetic resonance images. Moreover, the framework of functional MRI opened a window of opportunity to develop novel pathophysiologic markers. This article reviews applications of some well validated functional MRI techniques, including perfusion, diffusion-weighted imaging, and blood oxygen level-dependent MRI, as well as some emerging new techniques such as magnetic resonance elastography, which might evolve into clinically useful tools.

Abstract: ObjectivesQuantitative myocardial perfusion imaging by computed tomography (CT) was recently introduced to calculate myocardial blood flow (MBF). Because absolute MBF thresholds may be affected by technique, methodology, and the microvasculature, we investigated whether a relative measure of MBF imp

Abstract: Ischemia is a common and deleterious secondary injury following traumatic brain injury (TBI). A great challenge for the treatment of TBI patients in the neurointensive care unit (NICU) is to detect early signs of ischemia in order to prevent further advancement and deterioration of the brain tissue. Today, several imaging techniques are available to monitor cerebral blood flow (CBF) in the injured brain such as positron emission tomography (PET), single-photon emission computed tomography, xenon computed tomography (Xenon-CT), perfusion-weighted magnetic resonance imaging (MRI), and CT perfusion scan. An ideal imaging technique would enable continuous non-invasive measurement of blood flow and metabolism across the whole brain. Unfortunately, no current imaging method meets all these criteria. These techniques offer snapshots of the CBF. MRI may also provide some information about the metabolic state of the brain. PET provides images with high resolution and quantitative measurements of CBF and metabolism; however, it is a complex and costly method limited to few TBI centers. All of these methods except mobile Xenon-CT require transfer of TBI patients to the radiological department. Mobile Xenon-CT emerges as a feasible technique to monitor CBF in the NICU, with lower risk of adverse effects. Promising results have been demonstrated with Xenon-CT in predicting outcome in TBI patients. This review covers available imaging methods used to monitor CBF in patients with severe TBI.

Abstract: Standard imaging in acute stroke is undertaken with the aim of diagnosing the underlying cause and excluding stroke mimics. In the presence of ischaemic stroke, imaging is also needed to assess patient suitability for treatment with intravenous thrombolysis. Non-contrast CT is predominantly used, but MRI can also exclude any contraindications to thrombolysis treatment. Advanced stroke imaging such as CT and MR angiography and perfusion imaging are increasingly used in an acute setting. In this review, we discuss the evidence for the application of these advanced techniques in the imaging of acute stroke.

Abstract: Peripheral arterial disease (PAD) affects 27 million individuals in Europe and North America.1 This condition causes a severe restriction of blood flow that can lead to critical limb ischemia (CLI), a condition characterized by rest pain, ulceration, or gangrene, which is associated with limb loss in ≈25% of cases.2 The ischemic limb can be revascularized by endovascular techniques (angioplasty/stenting) or surgical bypass. Imaging modalities, including duplex ultrasound, MR angiography, computer tomographic angiography, or intra-arterial angiography, are used to assess the extent of disease, plan intervention, and confirm the patency of major blood vessels after intervention. These techniques do not provide information about perfusion at the tissue level. An early relatively crude method for assessing ischemic limbs, venous occlusion plethysmography3 relies on the principle that the volume of the limb is dependent on the arterial inflow when venous drainage is occluded. Under resting conditions, ≤70% of blood flow to the limb is directed to skeletal muscle, with the remainder to the skin circulation.4 Venous occlusion plethysmography provides a global indication of limb perfusion but gives no anatomic information and cannot delineate segmental perfusion deficits. It is influenced by numerous factors, such as ambient temperature and arteriovenous shunting that may lead to erroneous readings. Objective measurement of limb perfusion would particularly benefit patients with CLI but most attempts at addressing this have used patients with claudication. The latter can lead to CLI but is a less severe form of PAD that is often treated conservatively and is characterized by pain only when walking as opposed to pain at rest or gangrene. An accurate, noninvasive method of measuring limb perfusion would aid the diagnosis and treatment of PAD and could be combined with conventional angiography to provide both functional …

Abstract: Background/Purpose: Perfusion computed tomography (CT) is capable of measuring the permeability surface product (PS). PS reflects the permeability of the blood-brain barrier, involved in the pathophysiology of hemorrhagic transformation (HT) of ischemic stroke. The aim of our study was to determine if an increased PS can predict HT. Methods: A total of 86 patients with ischemic stroke were included. They underwent multimodality CT, including the measurement of PS. We compared the clinical and radiological characteristics of patients who developed HT to those who did not, using univariate analysis. Multivariate regression analyses were then used to determine HT predictors. Results: HT was observed in 27 patients (31%). Infarct PS was significantly associated with HT (p = 0.047), as were atrial fibrillation (p = 0.03), admission National Institute of Health Stroke Scale score (p = 0.02), infarct volume (p = 0.0004), presence of large-vessel occlusion (p = 0.0005) and a poorer collateral status (p = 0.003). Using logistic regression modeling, an infarct PS >0.84 ml/100 g/min was an independent predictor of HT (OR 28, 95% CI 1.75-452.98; p = 0.02). Other independent predictors of HT were infarct volume and a history of atrial fibrillation. Conclusions: Our findings suggest that infarct PS can be a predictor of HT and may help clinicians to improve patient care around thrombolysis decisions in the acute phase of ischemic stroke.

Abstract: Background: Prediction of clinical outcome in the acute stage of ischaemic stroke can be difficult when based on patient characteristics, clinical findings and on non-contrast CT. CT perfusion and CT angiography may provide additional prognostic information and guide treatment in the early stage. We present the study protocol of the Dutch acute Stroke Trial (DUST). The DUST aims to assess the prognostic value of CT perfusion and CT angiography in predicting stroke outcome, in addition to patient characteristics and non-contrast CT. For this purpose, individualised prediction models for clinical outcome after stroke based on the best predictors from patient characteristics and CT imaging will be developed and validated. Methods/design: The DUST is ap rospective multi-centre cohort study in 1500 patients with suspected acute ischaemic stroke. All patients undergo non-contrast CT, CT perfusion and CT angiography within 9 hours after onset of the neurological deficits, and, if possible, follow-up imaging after 3 days. The primary outcome is a dichotomised score on the modified Rankin Scale, assessed at 90 days. A score of 0–2 represents good outcome, and a score of 3–6 represents poor outcome. Three logistic regression models will be developed, including patient characteristics and non-contrast CT (model A), with addition of CT angiography (model B), and CT perfusion parameters (model C). Model derivation will be performed in 60% of the study population, and model validation in the remaining 40% of the patients. Additional prognostic value of the models will be determined with the area under the curve (AUC) from the receiver operating characteristic (ROC) curve, calibration plots, assessment of goodness-of-fit, and likelihood ratio tests. Discussion: This study will provide insight in the added prognostic value of CTP and CTA parameters in outcome prediction of acute stroke patients. The prediction models that will be developed in this study may help guide future treatment decisions in the acute stage of ischaemic stroke.

Abstract: Recent technical developments have significantly increased the SNR of arterial spin labeled (ASL) perfusion MRI. Despite this, typical ASL acquisitions still employ large voxel sizes. The purpose of this work was to implement and evaluate two ASL sequences optimized for whole-brain high-resolution perfusion imaging, combining pseudo-continuous ASL (pCASL), background suppression (BS) and 3D segmented readouts, with different in-plane k-space trajectories. Identical labeling and BS pulses were implemented for both sequences. Two segmented 3D readout schemes with different in-plane trajectories were compared: Cartesian (3D GRASE), and spiral (3D RARE Stack-Of-Spirals). High-resolution perfusion images (2×2×4 mm3) were acquired in fifteen young healthy volunteers with the two ASL sequences at 3T. The quality of the perfusion maps was evaluated in terms of SNR and gray-to-white matter contrast. Point-spread-function simulations were carried out to assess the impact of readout differences on the effective resolution. The combination of pCASL, in-plane segmented 3D readouts and BS provided high-SNR high-resolution ASL perfusion images of the whole brain. Although both sequences produced excellent image quality, the 3D RARE Stack-Of-Spirals readout yielded higher temporal and spatial SNR than 3D GRASE (Spatial SNR = 8.5 ± 2.8 and 3.7 ± 1.4; Temporal SNR = 27.4 ± 12.5 and 15.6 ± 7.6, respectively) and decreased through-plane blurring due to its inherent oversampling of the central k-space region, its reduced effective TE and shorter total readout time, at the expense of a slight increase in the effective in-plane voxel size.