Quantitative Blood Flow Measurements Research Articles

Quantitative blood flow measurement in rat brain with multiphase arterial spin labelling magnetic resonance imaging

Cerebral blood flow is an important parameter in many diseases and functional studies that can be accurately measured in humans using arterial spin labelling (ASL) MRI. However, although rat models are frequently used for preclinical studies of both human disease and brain function, rat CBF measurements show poor consistency between studies. This lack of reproducibility is due, partly, to the smaller size and differing head geometry of rats compared to humans, as well as the differing analysis methodologies employed and higher field strengths used for preclinical MRI. To address these issues, we have implemented, optimised and validated a multiphase pseudo-continuous ASL technique, which overcomes many of the limitations of rat CBF measurement. Three rat strains (Wistar, Sprague Dawley and Berlin Druckrey IX) were used, and CBF values validated against gold-standard autoradiography measurements. Label positioning was found to be optimal at 45°, while post-label delay was optimised to 0.55 s. Whole brain CBF measures were 109 ± 22, 111 ± 18 and 100 ± 15 mL/100 g/min by multiphase pCASL, and 108 ± 12, 116 ± 14 and 122 ± 16 mL/100 g/min by autoradiography in Wistar, SD and BDIX cohorts, respectively. Tumour model analysis shows that the developed methods also apply in disease states. Thus, optimised multiphase pCASL provides robust, reproducible and non-invasive measurement of CBF in rats.

ABNORMAL MYOCARDIAL BLOOD FLOW WITH NORMAL QUALITATIVE PERFUSION WITH POSITRON EMISSION TOMOGRAPHY MYOCARDIAL PERFUSION IMAGING IN HEART TRANSPLANT RECIPIENTS

Myocardial perfusion imaging (MPI) is often used to evaluate for cardiac allograft vasculopathy (CAV) in heart transplant recipients, but the accuracy of qualitative perfusion for CAV is unclear. Quantitative myocardial blood flow measurement with positron emission tomography (PET) may offer

Hybrid PET/MRI imaging in healthy unsedated newborn infants with quantitative rCBF measurements using 15O-water PET

In this study, a new hybrid PET/MRI method for quantitative regional cerebral blood flow (rCBF) measurements in healthy newborn infants was assessed and the low values of rCBF in white matter previously obtained by arterial spin labeling (ASL) were tested. Four healthy full-term newborn subjects were scanned in a PET/MRI scanner during natural sleep after median intravenous injection of 14 MBq 15O-water. Regional CBF was quantified using a one-tissue-compartment model employing an image-derived input function (IDIF) from the left ventricle. PET rCBF showed the highest values in the thalami, mesencephalon and brain stem and the lowest in cortex and unmyelinated white matter. The average global CBF was 17.8 ml/100 g/min. The average frontal and occipital unmyelinated white matter CBF was 10.3 ml/100 g/min and average thalamic CBF 31.3 ml/100 g/min. The average white matter/thalamic ratio CBF was 0.36, significantly higher than previous ASL data. The rCBF ASL measurements were all unsuccessful primarily owing to subject movement. In this study, we demonstrated for the first time, a minimally invasive PET/MRI method using low activity 15O-water PET for quantitative rCBF assessment in unsedated healthy newborn infants and found a white/grey matter CBF ratio similar to that of the adult human brain.

Quantitative pulmonary blood flow measurement using 15O-H2O PET with and without tissue fraction correction: a comparison study

BackgroundPhysiological measures per lung parenchyma, rather than per lung volume, sometimes reflect the disease status. PET images of the lung, which are usually expressed per lung volume, could confound the interpretation of the disease status, especially in cases with a prominent heterogeneity in aeration. The aim of the present study was to develop a method for measuring pulmonary blood flow (PBF) with aeration correction using 15O-H2O PET and to compare the results with those obtained using a conventional method. We obtained the voxel-based tissue fraction (TF) derived from density images converted from transmission images obtained using an external 137Cs point source. Quantitative PBF values with and without the TF were calculated using 15O-H2O PET to examine contralateral lung tissue in 9 patients with unilateral lung cancer. The heterogeneity in PBF before and after TF correction was then evaluated and compared. As a measure of PBF heterogeneity, we used the skewness and kurtosis of the PBF distribution.ResultsThe mean PBF of contralateral lung was 1.4 ± 0.3 mL/min per mL of lung. The TF-corrected PBF was 5.0 ± 0.6 mL/min per mL of lung parenchyma. After TF correction, the skewness and kurtosis of the PBF decreased significantly.ConclusionsThe present PBF calculation method using TF correction demonstrated that the normal PBF increased significantly and the PBF distribution became uniform. The proposed TF correction method is a promising technique to account for variations in density when interpreting PBF in PET studies.

An investigation of regional cerebral blood flow and tissue structure changes after acute administration of antipsychotics in healthy male volunteers.

Chronic administration of antipsychotic drugs has been linked to structural brain changes observed in patients with schizophrenia. Recent MRI studies have shown rapid changes in regional brain volume following just a single dose of these drugs. However, it is not clear if these changes represent real volume changes or are artefacts ("apparent" volume changes) due to drug-induced physiological changes, such as increased cerebral blood flow (CBF). To address this, we examined the effects of a single, clinical dose of three commonly prescribed antipsychotics on quantitative measures of T1 and regional blood flow of the healthy human brain. Males (n = 42) were randomly assigned to one of two parallel groups in a double-blind, placebo-controlled, randomized, three-period cross-over study design. One group received a single oral dose of either 0.5 or 2 mg of risperidone or placebo during each visit. The other received olanzapine (7.5 mg), haloperidol (3 mg), or placebo. MR measures of quantitative T1, CBF, and T1-weighted images were acquired at the estimated peak plasma concentration of the drug. All three drugs caused localized increases in striatal blood flow, although drug and region specific effects were also apparent. In contrast, all assessments of T1 and brain volume remained stable across sessions, even in those areas experiencing large changes in CBF. This illustrates that a single clinically relevant oral dose of an antipsychotic has no detectable acute effect on T1 in healthy volunteers. We further provide a methodology for applying quantitative imaging methods to assess the acute effects of other compounds on structural MRI metrics. Hum Brain Mapp 39:319-331, 2018. © 2017 Wiley Periodicals, Inc.

Evaluation of ghrelin levels and endothelial functions in patients with coronary slow flowphenomenon.

BackgroundGhrelin has recently been reported to have beneficial effects on cardiac contractile functions and coronary blood flow. The main purpose of this study was to investigate the role of ghrelin in the pathogenesis of coronary slow flow (CSF) together with endothelial functions.MethodsTwenty-five patients having normal coronary arteries with CSF and 25 controls with normal coronary flow were included into the study. The quantitative measurement of coronary blood flow was performed for each coronary artery using the thrombolysis in myocardial infarction (TIMI) frame count (TFC) method. Ghrelin levels were measured using the enzyme-linked immunosorbent assay method from venous blood samples. Endothelial functions were evaluated from the brachial artery with the flow-mediated dilation (FMD) and nitrate-related dilation methods.ResultsThere was a significant difference in terms of mean TFC values between the control and CSF groups (p < 0.001 for all coronary arteries). The mean FMD percentage among patients with CSF was lower than that of the control group (5.9 ± 0.8 vs. 10.7% ± 1.1%; p < 0.001). A moderate negative correlation was observed between the FMD percentages and the TFCs. There was no relationship between the TFC and ghrelin levels.ConclusionPlasma ghrelin levels seem to be uninfluential while impaired endothelial functions play an important role in the etiopathogenesis of CSF.

Measurement of retinal blood flow using Doppler OCT in diabetic retinopathy

SummaryPurposeTo determine factors of importance for quantitating retinal blood flow in patients with diabetic retinopathy using bi‐directional Doppler OCT.MethodsRetinal blood flow was measured by bi‐directional Doppler OCT in 20 diabetic patients with different diabetes type, age and retinopathy stage.ResultsIt appeared that age above 40 years was a significant limiting factor for obtaining suitable signals to measure retinal blood flow, which was due to lens opacities and insufficient mydriasis. Quantitative measures of blood flow in the studied patients below the age of 40 years will be reported.ConclusionBi‐directional Doppler OCT offers a new principle for quantitating retinal blood flow, but the principle has not yet been fully developed to be suitable for routine clinical practise.

Simulated Measurements of the Magnetic Behavior of New Dual-Mode Nanosized Contrast Agents

Aim of this work was to perform simulated measurements of the magnetic behavior of a novel class of bimodal nanosized contrast agents (CAs), made of a silica core covered by smaller superparamagnetic nanoparticles (NPs) and designed to be detected through both ultrasound and magnetic resonance imaging (MRI), in order to compare their performance in terms of MRI signal enhancement with that of the superparamagnetic NPs alone. The considered bimodal nanocomposites consisted of 330-nm silica nanospheres covered by either superparamagnetic iron oxide NPs or dumbbell-like FePt-IO nanocrystals. We simulated the MRI signal generated by each of the considered CAs during a brain venography in standard clinical conditions. Quantitative assessments of signal enhancement were carried out as a function of the main model parameters. The performed numerical simulations showed that the magnetic response of the novel nanocomposites was similar or better compared to that of the superparamagnetic NPs alone for echo times longer than 20 ms, leading to an easier detection of smaller vessels. Obtained results suggest that the bimodal NPs have an exciting potential for the development of innovative clinical protocols for multimodal imaging, combining quantitative measurements of cerebral blood flow and targeted molecular imaging of specific diseases.

Discrimination between patients with mild Alzheimer's disease and healthy subjects based on cerebral blood flow images of the lateral views in xenon-enhanced computed tomography.

Quantitative cerebral blood flow (CBF) measurement is expected to help early detection of functional abnormalities caused by Alzheimer's disease (AD) and enable AD treatment to begin in its early stages. Recently, a technique of layer analysis was reported that allowed CBF to be analyzed from the outer to inner layers of the brain. The aim of this work was to develop methods for discriminating between patients with mild AD and healthy subjects based on CBF images of the lateral views created with the layer analysis technique in xenon-enhanced computed tomography. Xenon-enhanced computed tomography using a wide-volume CT was performed on 17 patients with mild AD aged 75 or older and on 15 healthy age-matched volunteers. For each subject, we created CBF images of the right and left lateral views with a depth of 10-15 mm from the surface of the brain. Ten circular regions of interest (ROI) were placed on each image, and CBF was calculated for each ROI. We determined discriminant ROI that had CBF that could be used to differentiate between the AD and volunteer groups. AD patients' CBF range (mean - SD to mean + SD) and healthy volunteers' CBF range (mean - SD to mean + SD) were obtained for each ROI. Receiver-operator curves were created to identify patients with AD for each of the discriminant ROI and for the AD patients' and healthy volunteers' CBF ranges. We selected an ROI on both the right and left temporal lobes as the discriminant ROI. Areas under the receiver-operator curve were 93.3% using the ROI on the right temporal lobe, 95.3% using the ROI on the left temporal lobe, and 92.4% using the AD patients' and healthy volunteers' CBF ranges. We could effectively discriminate between patients with mild AD and healthy subjects using ROI placed on CBF images of the lateral views in xenon-enhanced computed tomography.

Reduced Cerebral Blood Flow in Mild Cognitive Impairment Assessed Using Phase-Contrast MRI.

There is increasing evidence of a vascular contribution to Alzheimer's disease (AD). In some cases, prior work suggests that chronic brain hypoperfusion could play a prime pathogenic role contributing to the accumulation of amyloid-β,while other studies favor the hypothesis that vascular dysfunction and amyloid pathology are independent, although synergistic, mechanisms contributing to cognitive impairment. Vascular dysfunction can be evaluated by assessing cerebral blood flow impairment. Phase contrast velocity mapping by MRI offers a non-invasive means of quantifying the total inflow of blood to the brain. This quantitative parameter could be a sensitive indicator of vascular disease at early stages of AD. In this work, phase contrast MRI was used to evaluate cerebral hemodynamics in patients with subjective memory complaints, amnestic mild cognitive impairment, and mild to moderate AD, and compare them with control subjects. Results showed that blood flow and velocity were decreased in the patients with cognitive dysfunction and the decrease correlated with the degree of cognitive impairment as assessed by means of neuropsychological tests. Total cerebral blood flow measurements were clearly reduced in AD patients, but more importantly appeared to be sensitive enough to distinguish between healthy subjects and those with mild cognitive impairment. A quantitative measurement of total brain blood flow could potentially predict vascular dysfunction and compromised brain perfusion in early stages of AD.

Acute cardiac support with intravenous milrinone promotes recovery from early brain injury in a murine model of severe subarachnoid haemorrhage.

Early brain injury/ischaemia (EBI) is a serious complication early after subarachnoid haemorrhage (SAH) that contributes to development of delayed cerebral ischaemia (DCI). This study aimed to determine the role of inotropic cardiac support using milrinone (MIL) on restoring acute cerebral hypoperfusion attributable to EBI and improving outcomes after experimental SAH. Forty-three male C57BL/6 mice were assigned to either sham surgery (SAH-sham), SAH induced by endovascular perforation plus postconditioning with 2% isoflurane (Control), or SAH plus isoflurane combined with MIL with and without hypoxia-inducible factor inhibitor (HIF-I) pretreatment. Cardiac output (CO) during intravenous MIL infusion (0.25-0.75μg/kg/min) between 1.5 and 2.5hours after SAH induction was monitored with Doppler echocardiography. Magnetic resonance imaging (MRI)-continuous arterial spin labelling was used for quantitative cerebral blood flow (CBF) measurements. Neurobehavioral function was assessed daily by neurological score and open field test. DCI was analyzed 3days later by determining infarction on MRI. Mild reduction of cardiac output (CO) and global cerebral blood flow (CBF) depression were notable early after SAH. MIL increased CO in a dose-dependent manner (P<.001), which was accompanied by improved hypoperfusion, incidence of DCI and functional recovery than Control (P<.05). The neuroprotective effects afforded by MIL or Control were attenuated by hypoxia-inducible factor (HIF) inhibition (P<.05). These results suggest that MIL improves acute hypoperfusion by its inotropic effect, leading to neurobehavioral improvement in mice after severe SAH, in which HIF may be acting as a critical mediator.

Abstract 193: Real-time Quantitative Changes in Cerebral Blood Flow From Intra-arterial Vasodilator Treatment in Cerebral Vasospasm

Introduction: Intra-arterial (IA) vasodilators are key components in the treatment of cerebral vasospasm (CV) resulting from subarachnoid hemorrhage (SAH) and traumatic brain injury (TBI). Angiographic assessments of vessel caliber immediately after infusion, however, are unreliable metrics of treatment effect, and as a result there does not currently exist a clear biomarker against which to titrate treatment. Quantitative cerebral blood flow (CBF) measurements from angiographic images may better characterize treatment effect and provide real-time feedback to guide infusion protocols. Methods: From our prospectively maintained institutional registry, we identified patients treated with IA vasodilators in the anterior circulation for CV between July 2014 and June 2016. Angiograms were reviewed by an experienced neuro angiographer blinded to clinical data and subsequent imaging. Regions of interest (ROIs) were drawn by two experienced neuroimagers over the MCA territory. CBF maps were calculated automatically from immediate pre- and immediate post-infusion angiograms using perfusion angiography and averaged over the ROIs. Results: A total of 65 angiograms were evaluated from 22 patients treated with vasodilators for CV. Average age was 48 and 60% were female. Etiology of vasospasm included SAH in 83% (54/65), TBI in 14% (9/65) and stroke/vasculopathy in 3% (2/65) Degree of vasospasm varied from mild (20% (13/65)) to moderate ((62% (40/65)) and severe (18% (12/65)). All patients were treated with IA verapamil ranging from 5 mg to 30 mg over the course of 10-60 minutes. Immediate post-infusion angiograms demonstrated improved vascular caliber in 23% (15/65) cases. In comparison, CBF increased on average 11% (SD 49) after verapamil infusion. Verapamil dosage correlated with percent change in CBF (p&lt;0.05, Spearman’s correlation). Conclusions: Verapamil infusion resulted in increased CBF in patients with CV from SAH and TBI. Quantitative angiographic CBF may serve as an effective real-time biomarker of treatment efficacy.

Sonomorphological, gray scale and color Doppler flow imaging evaluation of ovarian lesions

Background: Ultrasonography (USG) is considered the primary imaging modality for confirmation of the ovarian origin of the mass and characterization of the nature of the mass as benign or malignant. However, when morphologic features alone are applied to the prediction of ovarian malignancy, there is a tendency to over diagnose malignant tumors because of a substantial overlap between malignant and benign-appearing masses. Transvaginal color Doppler imaging with pulsed Doppler spectral analysis improves the characterization of ovarian masses by means of quantitative blood flow measurements obtained from tumor vessels. Color Doppler ultrasound helps identify solid, vascularized components in a mass. Objectives: To evaluate prospectively the relative usefulness of color Doppler, spectral Doppler, and gray scale sonography in differentiating benign from malignant adnexal masses. Materials and Methods: Patients with abdominal lump were screened for sonography. If on sonography patient having ovarian lesion then detailed study was carried out by gray scale, color, power Doppler and by spectral waveform analysis. Morphologic indexing of the adnexal masses was performed using the Sassone score. Flow results were recorded as being absent or present and further characterized as normal or increased, vessel location, and arrangement. Results: A total of 50 patients with 53 adnexal masses were enrolled into the study. Benign lesions were common in premenopausal age (30 [81%]) and malignant lesions (10 [77%]) were more common in the postmenopausal state. 23 out of 49 masses were considered suspicious of malignancy (Sassone score = 9), of which, 18 were malignant (including bilateral ovarian metastasis as a separate lesion) and 8 were benign. The sonomorphologic evaluation following Sassone scoring system had a sensitivity of 90%, specificity 75%, positive predictive value (PPV) 69% and negative predictive value (NPV) 92%. The sensitivity, specificity, PPV, and NPV of gray scale USG alone were 70%, 72.22%, 58.33%, and 81.25% respectively. While for gray scale with combined color and spectral Doppler USG the values were 90%, 91.66%, 85.71%, and 94.28%, respectively. Conclusion: Adding color Doppler to conventional sonography produced a specificity and PPV higher than those of conventional sonography alone and so gray scale USG in combination with Color Doppler and Spectral Doppler is proposed as the first and foremost diagnostic modality in patients with ovarian lesions.

Quantitative Measurement of Cerebral Blood Flow in Enhanced Psedo-continuous Arterial Spin Labeling Perfusion Imaging in Patients with Intracranial Atherosclerotic Stenosis.

Objective To acquire cerebral blood flow (CBF) in patients with severe intracranial atherosclerotic stenosis with enhanced pseudo-continuous arterial spin labeling (e-pCASL) and compare it with the findings of dynamic susceptibility contrast-enhanced perfusion-weighted imaging (DSC PWI) and pseudo-continuous arterial spin labeling (pCASL). Methods A total of 39 consecutive patients with severe intracranial atherosclerotic stenosis were enrolled in this study. All these patients underwent e-pCASL, pCASL, and DSC PWI. Blood supply territory of the stenosed artery was outlined as region of interest (ROI) and a mirror ROI was applied. Ratios of CBF were calculated as value of ROI/value of mirror ROI. SNK variance analysis was conducted to compare the CBF values of three persufion methods. Factorial analysis of variance and Pearson were employed to analysis the difference and the correlation of e-pCASL CBF ratio, pCASL CBF ratio, and DSC PWI relative cerebral blood flow(rCBF) ratio. Results The e-pCASL CBF ratio, pCASL CBF ratio, and DSC PWI rCBF ratio were not significantly different (P=0.476). TTP showed the CBF ratios were not significantly different between the healthy side and diseased side in patients with severe intracranial atherosclerotic stenosis. ATT showed the correlations of pCASL CBF ratio and DSC PWI rCBF ratio were not affected by ATT. Conclusions e-pCASL with multiple-post labeling delay time and pCASL have good consistency with DSC PWI in the quantitative measurement of hypoperfusion pattern. As an accurate, simple, non-invasive, and repeatable technique, e-pCASL has good correlation with DSC PWI in the quantitative measurement of hypoperfusion pattern that is not affected by ATT.

A look-locker acquisition scheme for quantitative myocardial perfusion imaging with FAIR arterial spin labeling in humans at 3 tesla.

PurposeA novel method for quantitative measurement of myocardial blood flow (MBF) using arterial spin labeling (ASL) in a single breath‐hold is presented, evaluated by simulations, phantom studies and in vivo studies and tested for reproducibility and variability.MethodsA flow‐sensitive alternating inversion recovery (FAIR) ASL method with Look‐Locker readout (LL‐FAIR‐ASL) was implemented at 3 tesla. Scans were performed on 10 healthy volunteers and MBF measured in three slices. The method was investigated for reproducibility by Bland‐Altman analysis and statistical measures, the coefficients of reproducibility (CR) and variation (CV) are reported.ResultsThe MBF values for the basal, mid, and apical slices were 1.04 ± 0.40, 1.06 ± 0.46, and 1.06 ± 0.38 ml/g/min, respectively (mean ± SD), which compare well with literature values. The CV across all scans, 43%, was greater than the between‐session and within‐session values, at 16 and 13%, respectively, for the mid‐ventricular slice. The change in MBF required for detection, from the CR, was 61% between‐session and 53% within‐session for the mid‐ventricle.ConclusionThis study shows the feasibility of the LL‐FAIR‐ASL method for the quantification of MBF. The statistical measures reported will allow the planning of future clinical research studies involving rest and stress measurements. Magn Reson Med 78:541–549, 2017. © 2016 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Surgical fiducial segmentation and tracking for pose estimation based on ultrasound B-mode images.

Doppler ultrasound is a non-invasive diagnostic tool for the quantitative measurement of blood flow. However, given that it provides velocity data that is dependent on the location and angle of measurement, repeat measurements to detect problems over time may require an expert to return to the same location. We therefore developed an image-guidance system based on ultrasound B-mode images that enables an inexperienced user to position the ultrasound probe at the same site repeatedly in order to acquire a comparable time series of Doppler readings. The system utilizes a bioresorbable fiducial and complementing software composed of the fiducial detection, key points tracking, probe pose estimation, and graphical user interface (GUI) modules. The fiducial is an echogenic marker that is implanted at the surgical site and can be detected and tracked during ultrasound B-mode screening. The key points on the marker can next be used to determine the pose of the ultrasound probe with respect to the marker. The 3D representation of the probe with its position and orientation are then displayed in the GUI for the user guidance. The fiducial detection has been tested on the data sets collected from three animal studies. The pose estimation algorithm was validated by five data sets collected by a UR5 robot. We tested the system on a plastisol phantom and showed that it can detect and track the fiducial marker while displaying the probe pose in real-time.

Aerobic fitness is associated with greater hippocampal cerebral blood flow in children

The present study is the first to investigate whether cerebral blood flow in the hippocampus relates to aerobic fitness in children. In particular, we used arterial spin labeling (ASL) perfusion MRI to provide a quantitative measure of blood flow in the hippocampus in 73 7- to 9-year-old preadolescent children. Indeed, aerobic fitness was found to relate to greater perfusion in the hippocampus, independent of age, sex, and hippocampal volume. Such results suggest improved microcirculation and cerebral vasculature in preadolescent children with higher levels of aerobic fitness. Further, aerobic fitness may influence how the brain regulates its metabolic demands via blood flow in a region of the brain important for learning and memory. To add specificity to the relationship of fitness to the hippocampus, we demonstrate no significant association between aerobic fitness and cerebral blood flow in the brainstem. Our results reinforce the importance of aerobic fitness during a critical period of child development.

Integration of Quantitative Positron Emission Tomography Absolute Myocardial Blood Flow Measurements in the Clinical Management of Coronary Artery Disease.

In the >40 years since planar myocardial imaging with(43)K-potassium was introduced into clinical research and management of patients with coronary artery disease (CAD), diagnosis and treatment have undergone profound scientific and technological changes. One such innovation is the current state-of-the-art hardware and software for positron emission tomography myocardial perfusion imaging, which has advanced it from a strictly research-oriented modality to a clinically valuable tool. This review traces the evolving role of quantitative positron emission tomography measurements of myocardial blood flow in the evaluation and management of patients with CAD. It presents methodology, currently or soon to be available, that offers a paradigm shift in CAD management. Heretofore, radionuclide myocardial perfusion imaging has been primarily qualitative or at best semiquantitative in nature, assessing regional perfusion in relative terms. Thus, unlike so many facets of modern cardiovascular practice and CAD management, which depend, for example, on absolute values of key parameters such as arterial and left ventricular pressures, serum lipoprotein, and other biomarker levels, the absolute levels of rest and maximal myocardial blood flow have yet to be incorporated into routine clinical practice even in most positron emission tomography centers where the potential to do so exists. Accordingly, this review focuses on potential value added for improving clinical CAD practice by measuring the absolute level of rest and maximal myocardial blood flow. Physiological principles and imaging fundamentals necessary to understand how positron emission tomography makes robust, quantitative measurements of myocardial blood flow possible are highlighted.

Comparison of quantitative myocardial perfusion imaging CT to fluorescent microsphere-based flow from high-resolution cryo-images.

Myocardial perfusion imaging using CT (MPI-CT) has the potential to provide quantitative measures of myocardial blood flow (MBF) which can aid the diagnosis of coronary artery disease. We evaluated the quantitative accuracy of MPI-CT in a porcine model of balloon-induced LAD coronary artery ischemia guided by fractional flow reserve (FFR). We quantified MBF at baseline (FFR=1.0) and under moderate ischemia (FFR=0.7) using MPI-CT and compared to fluorescent microsphere-based MBF from high-resolution cryo-images. Dynamic, contrast-enhanced CT images were obtained using a spectral detector CT (Philips Healthcare). Projection-based mono-energetic images were reconstructed and processed to obtain MBF. Three MBF quantification approaches were evaluated: singular value decomposition (SVD) with fixed Tikhonov regularization (ThSVD), SVD with regularization determined by the L-Curve criterion (LSVD), and Johnson-Wilson parameter estimation (JW). The three approaches over-estimated MBF compared to cryo-images. JW produced the most accurate MBF, with average error 33.3±19.2mL/min/100g, whereas LSVD and ThSVD had greater over-estimation, 59.5±28.3mL/min/100g and 78.3±25.6 mL/min/100g, respectively. Relative blood flow as assessed by a flow ratio of LAD-to-remote myocardium was strongly correlated between JW and cryo-imaging, with R2=0.97, compared to R2=0.88 and 0.78 for LSVD and ThSVD, respectively. We assessed tissue impulse response functions (IRFs) from each approach for sources of error. While JW was constrained to physiologic solutions, both LSVD and ThSVD produced IRFs with non-physiologic properties due to noise. The L-curve provided noise-adaptive regularization but did not eliminate non-physiologic IRF properties or optimize for MBF accuracy. These findings suggest that model-based MPI-CT approaches may be more appropriate for quantitative MBF estimation and that cryo-imaging can support the development of MPI-CT by providing spatial distributions of MBF.

Quantitative measurement of blood flow in paediatric brain tumours-a comparative study of dynamic susceptibility contrast and multi time-point arterial spin labelled MRI.

Objective:Arterial spin-labelling (ASL) MRI uses intrinsic blood water to quantify the cerebral blood flow (CBF), removing the need for the injection of a gadolinium-based contrast agent used for conventional perfusion imaging such as dynamic susceptibility contrast (DSC). Owing to the non-invasive nature of the technique, ASL is an attractive option for use in paediatric patients. This work compared DSC and multi-timepoint ASL measures of CBF in paediatric brain tumours.Methods:Patients (n = 23; 20 low-grade tumours and 3 high-grade tumours) had DSC and multi-timepoint ASL with and without vascular crushers (VC). VC removes the contribution from larger vessel blood flow. Mean perfusion metrics were extracted from control and T1-enhanced tumour regions of interest (ROIs): arterial arrival time (AAT) and CBF from the ASL images with and without VC, relative cerebral blood flow (rCBF), relative cerebral blood volume, delay time (DT) and mean transit time (MTT) from the DSC images.Results:Significant correlations existed for: AAT and DT (r = 0.77, p = 0.0002) and CBF and rCBF (r = 0.56, p = 0.02) in control ROIs for ASL-noVC. No significant correlations existed between DSC and ASL measures in the tumour region. Significant differences between control and tumour ROI were found for MTT (p < 0.001) and rCBF (p < 0.005) measures.Conclusion:Significant correlations between ASL-noVC and DSC measures in the normal brain suggest that DSC is most sensitive to macrovascular blood flow. The absence of significant correlations within the tumour ROI suggests that ASL is sensitive to different physiological mechanisms compared with DSC measures.Advances in knowledge:ASL provides information which is comparable with that of DSC in healthy tissues, but appears to reflect a different physiology in tumour tissues.