Article

Equations for Measuring Blood Flow by External Monitoring of Radioisotopes

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Abstract

It is possible by external monitoring alone to measure blood flow per unit volume through any vascular bed accessible to external monitoring of the radioactive tracer if the tracer input function or if the quantity of tracer entering the system is known. The methods proposed exploit the fact that the mean transit time through the system is the flow per unit volume of distribution of tracer. The equations are free of assumptions that require solutions as exponentials or any other specified frequency function of transit times. If the input function is known, measurement of the concentration of tracer in blood leaving the part sensed by the external detector, combined with external detection of radioactivity, can lead to measurement of absolute blood flow.

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... It is also the second most common reason for hospitalization in Singapore [2]. In the recent few decades, extensive studies have been conducted on microcirculation systems for tumor characterization and diagnosis, in both academic institutions and commercial companies [3][4][5][6][7][8][9]. Such studies rely on the observation of microvascular transport ...
... injected at the arterial inlet as depicted in approaches zero gradually as time passes [6,10,11,56]. The correlation between and can be explained by ...
... From a statistical viewpoint, suggests a certain probability of the tracer taking a transit time t to pass through the system. As a result, describes the transit time distribution [6,10,11]. The tracer Mean Transit Time (MTT) is thus given by ...
Thesis
This thesis focuses on the investigation of Dynamic Contrast-Enhanced (DCE) based parametric assessment methods for tumor characterization, diagnosis and prognosis. In the recent few decades, extensive studies have been done on parametric assessments of tumor microcirculation characteristics. The introduction of DCE technique further enables the determination of relevant tumor microcirculation parameters, such as blood flow, blood volume, and capillary permeability. Early empirical model-free methods using DCE imaging are fast and simple in parameter assessment but their theoretical ground is insufficient. To model tracer concentration-time curves in a more systematic way, tracer kinetic models have been developed. However, practical applications of existing models are constrained by imprecise mathematical representation, unreliable parameter estimation, and high computational complexity. To addresses these issues, the research reported in this study proposes novel solutions using theoretical, numerical, and experimental techniques. Firstly, an Infinite-Pathways Distributed Parameter (IPDP) model was developed. It originates from the multiple-pathway model by Bassingthwaighte et al. and inherits the advantage of blood flow variability assessment. Through reconstructing the mathematical representation of the vasculature network, the IPDP model eliminates the discontinuities and normalization errors in multiple-pathway model, and at the same time relieves the dependency on hardware performance. The reconstruction of mathematical representation also enables in vivo assessment of blood flow distribution with DCE imaging. The IPDP model was assessed by applying on patient data with cerebral tumors. Estimation results clearly show the properties of capillary-tissue units and distinguish tumor tissues from normal tissues effectively. Secondly, a study using the proposed IPDP model was made to evaluate the performance of empirical model-free methods. The results obtained show that the accuracy of empirical methods is condition-dependent and some conditions may be difficult to meet in practice. The results also suggest that the peak enhancement metrics are not linearly related to any intrinsic tissue parameters. Thirdly, an improvement was made on the reliability of parameter estimation using the IPDP model. Studies have shown that the model-fitting process is sometimes trapped in a local minimum that is far from the global minimum, and it generates undesired results. A dual-phase model-fitting method was proposed to drive the model-fitting process towards global minimum for tracer enhancement curves with a washout pattern. Numerical results show that the coefficient of variation using the proposed approach can be reduced by up to 83% and the estimation bias is also alleviated in general. The proposed approach is applicable in blood flow dominated cases and could be implemented in existing tracer kinetic models for more accurate and stable parameter extraction. Finally, an attempt was made to reduce the computational complexity of the IPDP model. Specifically, a simplified Infinite-Pathway Conventional Compartmental (IPCC) model was developed by incorporating a conventional two-compartment model into each of the multiple pathways. The IPCC model was used to generate perfusion parameter maps for three DCE computed tomography patient cases to study its clinical applicability. The simplified IPCC model takes approximately 0.1s to generate an impulse response function compared to the 81s processing time by the original multiple-pathway software. Results also show that the simplified IPCC model has better fitting performance than the standard two-compartment model in most cases. In summary, the research conducted has led to the proposal of advanced tracer kinetic models. IPDP model improves the mathematic representation of the existing multiple-pathway kinetic models. Using the IPDP model, an in-depth study has been conducted on the performance and physiological implications of existing empirical model-free methods. Furthermore, the dual-phase model-fitting method and the IPCC model were proposed to reduce the coefficient of variations, estimation bias, and computational complexity of the IPDP model. The work reported in this thesis has offered desirable tracer kinetic models, modeling approach and algorithm for the characterization and diagnosis of cerebral tumor.
... This means that protons precede or follow their previous precession. As in the case of the readout 32 gradient, the phase difference depends on the magnitude and duration of the gradient as well as the proton position (described by equation 2-4) [8]. precessional frequency depending upon its position (equation [2][3][4]. ...
... Model-independent approaches are fundamentally based on the central volume principle which was first described by Zierler et al [32,33]. This is based on the principle introduced by Eugen Fick which states that the rate at which a substance aggregates in a tissue of interest can be given by the concentration difference of the contrast agent entering and leaving the region multiplied by the flow rate (F). ...
... This is based on the principle introduced by Eugen Fick which states that the rate at which a substance aggregates in a tissue of interest can be given by the concentration difference of the contrast agent entering and leaving the region multiplied by the flow rate (F). This can be mathematically described as [24,32,33]: where c in , c out are the contrast agent concentrations at the inlet and outlet of the region respectively, q(t) is the mass of the contrast agent and dq(t)/dt is its rate of change in time (t). This is a statement of mass balance which describes that the amount of contrast agent which has entered the tissue of interest and has not yet exited, has remained in the region of interest. ...
... Model-independent approaches rely on the indicator dilution theory introduced by Zierler 81 [37,106,107]. This principle considers a system composed of a single inlet and a single outlet through 82 which circulates a volume V of fluid at a constant rate of flow F. Its internal structure offers multiple 83 pathways so that a particle of fluid entering into the system can then use different ways to reach the 84 outlet with a variable dwell time inside the system; we let T be the mean transit time of a particle. ...
... The average CA concentration at the peak value 551 was 5.86 mmol/L at stress, which was slightly more substantial than that observed by Kellman et al. 36 552 but is consistent since only a dose of 0.05 mmol/kg was injected at a rate of 6 mL/s in this study 553 instead of a full dose of 0.2 mmol/kg injected at a rate of 4 mL/s. In their study 37 , which used a 3T 554 scanner similar to ours, Papanastasiou et al. measured AIF peak values ranging from 5.5 mmol/L to 555 6.5 mmol/L with identical injection parameters as was done in Kellman's study [117]. The noise 556 parameters were measured at the base of the LV myocardium at the different observation scale levels. ...
Thesis
Les maladies cardiovasculaires et en particulier les maladies coronariennes représentent la principale cause de mortalité mondiale avec 17,9 millions de décès en 2012. L’IRM cardiaque est un outil particulièrement intéressant pour la compréhension et l’évaluation des cardiopathies, notamment ischémiques. Son apport diagnostique est souvent majeur et elle apporte des informations non accessibles par d’autres modalités d’imagerie. Les travaux menés pendant cette thèse portent plus particulièrement sur l’examen dit de perfusion myocardique qui consiste à étudier la distribution d’un agent de contraste au sein du muscle cardiaque lors de son premier passage. En pratique clinique cet examen est souvent limité à la seule analyse visuelle du clinicien qui recherche un hyposignal lui permettant d’identifier l’artère coupable et d’en déduire le territoire impacté. Cependant, cette technique est relative et ne permet pas de quantifier le flux sanguin myocardique. Au cours de ces dernières années, un nombre croissant de techniques sont apparues pour permettre cette quantification et ce à toutes les étapes de traitement, depuis l’acquisition jusqu’à la mesure elle-même. Nous avons dans un premier temps établi un pipeline de traitement afin de combiner ces approches et de les évaluer à l’aide d’un fantôme numérique et à partir de données cliniques. Nous avons pu démontrer que l’approche Bayésienne permettait de quantifier la perfusion cardiaque et sa supériorité à évaluer le délai d’arrivé du bolus d’indicateur par rapport au modèle de Fermi. De plus l’approche Bayésienne apporte en supplément des informations intéressantes telles que la fonction de densité de probabilité de la mesure et l’incertitude sur la fonction résidu qui permettent de connaitre la fiabilité de la mesure effectuée notamment en observant la répartition de la fonction de densité de probabilité de la mesure. Enfin, nous avons proposé un algorithme de segmentation des lésions myocardiques, exploitant les dimensions spatiotemporelles des données de perfusion. Cette technique permet une segmentation objective et précise de la région hypoperfusée permettant une mesure du flux sanguin myocardique sur une zone de tissu dont le comportement est homogène et dont la mesure du signal moyen permet une augmentation du rapport contraste à bruit. Sur la cohorte de 30 patients, la variabilité des mesures du flux sanguin myocardique effectuées sur les voxels détectés par cette technique était significativement inférieure à celle des mesures effectuées sur les voxels des zones définies manuellement (différence moyenne=0.14, 95% CI [0.07, 0.2]) et de celles effectuées sur les voxels des zones définies à partir de la méthode bullseye (différence moyenne =0.25, 95% CI [0.17, 0.36])
... Quantitative perfusion maps are generated in-line on the MR imager or automatically through commercial postprocessing software (28)(29)(30). The perfusion quantification is based on the indicator dilution theory applied to cardiac MRI first-pass perfusion (50)(51)(52)(53)(54). ...
... Semiquantitative analysis can be performed by the upslope method (upslope of myocardial attenuation/upslope of the blood pool attenuation) (62,65). Fully quantitative perfusion measures myocardial blood flow in milliliters per gram per minute with postprocessing software and follows the principles of the indicator dilution theory (53,54,63). ...
Article
Ischemic heart disease is a leading cause of death worldwide and comprises a large proportion of annual health care expenditure. Management of ischemic heart disease is now best guided by the physiologic significance of coronary artery stenosis. Invasive coronary angiography is the standard for diagnosing coronary artery stenosis. However, it is expensive and has risks including vascular access site complications and contrast material-induced nephropathy. Invasive coronary angiography requires fractional flow reserve (FFR) measurement to determine the physiologic significance of a coronary artery stenosis. Multiple noninvasive cardiac imaging modalities can also anatomically delineate or functionally assess for significant coronary artery stenosis, as well as detect the presence of myocardial infarction (MI). While coronary CT angiography can help assess the degree of anatomic stenosis, its inability to assess the physiologic significance of lesions limits its specificity. Physiologic significance of coronary artery stenosis can be determined by cardiac MR vasodilator or dobutamine stress imaging, CT stress perfusion imaging, FFR CT, PET myocardial perfusion imaging (MPI), SPECT MPI, and stress echocardiography. Clinically unrecognized MI, another clear indicator of physiologically significant coronary artery disease, is relatively common and is best evaluated with cardiac MRI. The authors illustrate the spectrum of imaging findings of ischemic heart disease (coronary artery disease, myocardial ischemia, and MI); highlight the advantages and disadvantages of the various noninvasive imaging methods used to assess ischemic heart disease, as illustrated by recent clinical trials; and summarize current indications and contraindications for noninvasive imaging techniques for detection of ischemic heart disease. Online supplemental material is available for this article. Published under a CC BY 4.0 license.
... Indicator dilution techniques for determination of cerebral hemodynamic parameters have been investigated since the turn of the 19th century (43). A bolus injection of a dye into the bloodstream and the subsequent collection of the diluted sample formed the basis of the resulting formalism. ...
... The cumulative distribution function shown in Figure 12 is the integral of the transport function over time and represents the fraction of contrast that has left the voxel at time (t). Subsequently, the amount of contrast remaining in the voxel after time (t) is then defined as the residue function R(t) and is given by 1-H(t) (Fig. 12) (43). Ostergaard et al. showed through the use of the residue function that the CBF is then derived from the following equation, which is central to all semiquantitative approaches in DSC-MRI (56,57). ...
Chapter
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... Central to MBF quantification is the arterial input function (AIF) which describes the contrast agent input to the myocardium [10]. It has been known since early theoretical developments of tracer-based flow measurement that accurate quantification requires the AIF to be sampled at the true myocardial input [11,12]. However, imaging the relatively small coronary ostia is not a feasible option in CMR perfusion due to limitations of spatial resolution, which could result in severe partial volume effects exacerbated by cardiac and respiratory motion. ...
... These findings have important implications for the interpretation of CMR perfusion data and encourage standardization of quantitative analysis to ensure reproducibility of perfusion measurements. Quantification of perfusion is based on the indicatordilution theory that relates the amount of contrast agent inflow with outflow [11,12]. The principle postulates that all contrast agent molecules measured at the input location flow across the myocardial capillary bed and reach the output location, and therefore the principle assumes a single-input single-output system. ...
Article
Full-text available
Background: Quantification of myocardial blood flow (MBF) and myocardial perfusion reserve (MPR) by cardiovascular magnetic resonance (CMR) perfusion requires sampling of the arterial input function (AIF). While variation in the AIF sampling location is known to impact quantification by CMR and positron emission tomography (PET) perfusion, there is no evidence to support the use of a specific location based on their diagnostic accuracy in the detection of coronary artery disease (CAD). This study aimed to evaluate the accuracy of stress MBF and MPR for different AIF sampling locations for the detection of abnormal myocardial perfusion with expert visual assessment as the reference. Methods: Twenty-five patients with suspected or known CAD underwent vasodilator stress-rest perfusion with a dual-sequence technique at 3T. A low-resolution slice was acquired in 3-chamber view to allow AIF sampling at five different locations: left atrium (LA), basal left ventricle (bLV), mid left ventricle (mLV), apical left ventricle (aLV) and aortic root (AoR). MBF and MPR were estimated at the segmental level using Fermi function-constrained deconvolution. Segments were scored as having normal or abnormal perfusion by visual assessment and the diagnostic accuracy of stress MBF and MPR for each location was evaluated using receiver operating characteristic curve analysis. Results: In both normal (300 out of 400, 75 %) and abnormal segments, rest MBF, stress MBF and MPR were significantly different across AIF sampling locations (p < 0.001). Stress MBF for the AoR (normal: 2.42 (2.15-2.84) mL/g/min; abnormal: 1.71 (1.28-1.98) mL/g/min) had the highest diagnostic accuracy (sensitivity 80 %, specificity 85 %, area under the curve 0.90; p < 0.001 versus stress MBF for all other locations including bLV: normal: 2.78 (2.39-3.14) mL/g/min; abnormal: 2.22 (1.83-2.48) mL/g/min; sensitivity 91 %, specificity 63 %, area under the curve 0.81) and performed better than MPR for the LV locations (p < 0.01). MPR for the AoR (normal: 2.43 (1.95-3.14); abnormal: 1.58 (1.34-1.90)) was not superior to MPR for the bLV (normal: 2.59 (2.04-3.20); abnormal: 1.69 (1.36-2.14); p = 0.717). Conclusions: The AIF sampling location has a significant impact on MBF and MPR estimates by CMR perfusion, with AoR-based stress MBF comparing favorably to that for the current clinical reference bLV.
... Indicator dilution techniques for determination of cerebral hemodynamic parameters have been investigated since the turn of the 19th century (43). A bolus injection of a dye into the bloodstream and the subsequent collection of the diluted sample formed the basis of the resulting formalism. ...
... The cumulative distribution function shown in Figure 12 is the integral of the transport function over time and represents the fraction of contrast that has left the voxel at time (t). Subsequently, the amount of contrast remaining in the voxel after time (t) is then defined as the residue function R(t) and is given by 1-H(t) (Fig. 12) (43). Ostergaard et al. showed through the use of the residue function that the CBF is then derived from the following equation, which is central to all semiquantitative approaches in DSC-MRI (56,57). ...
Chapter
Full-text available
... 16 Mean transit time (MTT) was derived from the central volume principle as the ratio of cerebral blood volume to cerebral blood flow. 17 ...
Article
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Background and Purpose— Cerebral perfusion in acute ischemic stroke patients is often assessed before endovascular thrombectomy (EVT), but rarely after. Perfusion data obtained following EVT may provide additional prognostic information. We developed a tool to quantitatively derive perfusion measurements from digital subtraction angiography (DSA) data and examined perfusion in patients following EVT. Methods— Source DSA images from acute anterior circulation stroke patients undergoing EVT were retrospectively assessed. Following deconvolution, maps of mean transit time (MTT) were generated from post-EVT DSA source data. Thrombolysis in Cerebral Infarction grades and MTT in patients with and without hemorrhagic transformation (HT) at 24 hours were compared. Receiver operating characteristic modeling was used to classify the presence/absence of HT at 24 hours by MTT. Results— Perfusion maps were generated in 50 patients using DSA acquisitions that were a median (interquartile range) of 9 (8–10) seconds in duration. The median post-EVT MTT within the affected territory was 2.6 (2.2–3.3) seconds. HT was observed on follow-up computed tomography in 16 (32%) patients. Thrombolysis in Cerebral Infarction grades did not differ in patients with HT from those without ( P =0.575). Post-EVT MTT maps demonstrated focal areas of hyperperfusion (n=8) or persisting hypoperfusion (n=3) corresponding to the regions where HT later developed. The relationship between MTT and HT was U -shaped; HT occurred in patients at both the lowest and highest extremes of MTT. An MTT threshold <2 or >4 seconds was 81% sensitive and 94% specific for classifying the presence of HT at follow-up. Conclusions— Perfusion measurements can be obtained using DSA perfusion with minimal changes to current stroke protocols. Perfusion imaging post-recanalization may have additional clinical utility beyond visual assessment of source angiographic images alone.
... Stress and rest first-pass perfusion imaging will be performed using an echo planar imaging dual-sequence investigational perfusion method, which consists of a low resolution arterial input function image, followed by three short axis (base, mid and apex) myocardial images during each R-R interval. [40][41][42] Vasodilator stress will be achieved with adenosine infusion 140-210 µg/kg/min for 3 min. Resting first-pass perfusion will be performed at least 10 min later. ...
Article
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Introduction Angina with no obstructive coronary artery disease (ANOCA) is a common syndrome with unmet clinical needs. Microvascular and vasospastic angina are relevant but may not be diagnosed without measuring coronary vascular function. The relationship between cardiovascular magnetic resonance (CMR)-derived myocardial blood flow (MBF) and reference invasive coronary function tests is uncertain. We hypothesise that multiparametric CMR assessment will be clinically useful in the ANOCA diagnostic pathway. Methods/analysis The Stratified Medical Therapy Using Invasive Coronary Function Testing In Angina (CorMicA) trial is a prospective, blinded, randomised, sham-controlled study comparing two management approaches in patients with ANOCA. We aim to recruit consecutive patients with stable angina undergoing elective invasive coronary angiography. Eligible patients with ANOCA (n=150) will be randomised to invasive coronary artery function-guided diagnosis and treatment (intervention group) or not (control group). Based on these test results, patients will be stratified into disease endotypes: microvascular angina, vasospastic angina, mixed microvascular/vasospastic angina, obstructive epicardial coronary artery disease and non-cardiac chest pain. After randomisation in CorMicA, subjects will be invited to participate in the Coronary Microvascular Angina Cardiac Magnetic Resonance Imaging (CorCMR) substudy. Patients will undergo multiparametric CMR and have assessments of MBF (using a novel pixel-wise fully quantitative method), left ventricular function and mass, and tissue characterisation (T1 mapping and late gadolinium enhancement imaging). Abnormalities of myocardial perfusion and associations between MBF and invasive coronary artery function tests will be assessed. The CorCMR substudy represents the largest cohort of ANOCA patients with paired multiparametric CMR and comprehensive invasive coronary vascular function tests. Ethics/dissemination The CorMicA trial and CorCMR substudy have UK REC approval (ref.16/WS/0192). Trial registration number NCT03193294 .
... Before the determination of MBF, the correction procedure of the high concentration AIF was performed using the traditional dual bolus and the modified dual bolus methods. The modified dual bolus method is based on the Steward-Hamilton principle [23]. ...
Article
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Background: The reliable quantification of myocardial blood flow (MBF) with MRI, necessitates the correction of errors in arterial input function (AIF) caused by the T1 saturation effect. The aim of this study was to compare MBF determined by a traditional dual bolus method against a modified dual bolus approach and to evaluate both methods against PET in a porcine model of myocardial ischemia. Methods: Local myocardial ischemia was induced in five pigs, which were subsequently examined with contrast enhanced MRI (gadoteric acid) and PET (O-15 water). In the determination of MBF, the initial high concentration AIF was corrected using the ratio of low and high contrast AIF areas, normalized according to the corresponding heart rates. MBF was determined from the MRI, during stress and at rest, using the dual bolus and the modified dual bolus methods in 24 segments of the myocardium (total of 240 segments, five pigs in stress and rest). Due to image artifacts and technical problems 53% of the segments had to be rejected from further analyses. These two estimates were later compared against respective rest and stress PET-based MBF measurements. Results: Values of MBF were determined for 112/240 regions. Correlations for MBF between the modified dual bolus method and PET was rs = 0.84, and between the traditional dual bolus method and PET rs = 0.79. The intraclass correlation was very good (ICC = 0.85) between the modified dual bolus method and PET, but poor between the traditional dual bolus method and PET (ICC = 0.07). Conclusions: The modified dual bolus method showed a better agreement with PET than the traditional dual bolus method. The modified dual bolus method was found to be more reliable than the traditional dual bolus method, especially when there was variation in the heart rate. However, the difference between the MBF values estimated with either of the two MRI-based dual-bolus methods and those estimated with the gold-standard PET method were statistically significant.
... The AIF is the arterial concentration of contrast agent C a (t) representing the intravascular tracer delivery to the local capillary network. The tissue tracer concentration C(t) is proportional to the convolution of C a (t) with the tissue impulse response function, i.e., the tissue residue function R scaled by the CBF [20]: ...
Article
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Objective Deconvolution is an ill-posed inverse problem that tends to yield non-physiological residue functions R ( t ) in dynamic susceptibility contrast magnetic resonance imaging (DSC-MRI). In this study, the use of Bézier curves is proposed for obtaining physiologically reasonable residue functions in perfusion MRI. Materials and methods Cubic Bézier curves were employed, ensuring R (0) = 1, bounded-input, bounded-output stability and a non-negative monotonically decreasing solution, resulting in 5 parameters to be optimized. Bézier deconvolution (BzD), implemented in a Bayesian framework, was tested by simulation under realistic conditions, including effects of arterial delay and dispersion. BzD was also applied to DSC-MRI data from a healthy volunteer. Results Bézier deconvolution showed robustness to different underlying residue function shapes. Accurate perfusion estimates were observed, except for boxcar residue functions at low signal-to-noise ratio. BzD involving corrections for delay, dispersion, and delay with dispersion generally returned accurate results, except for some degree of cerebral blood flow (CBF) overestimation at low levels of each effect. Maps of mean transit time and delay were markedly different between BzD and block-circulant singular value decomposition (oSVD) deconvolution. Discussion A novel DSC-MRI deconvolution method based on Bézier curves was implemented and evaluated. BzD produced physiologically plausible impulse response, without spurious oscillations, with generally less CBF underestimation than oSVD.
... Indicator dilution theory was originally developed for measurement of cardiac output (Stewart, 1897), and has since been extended to flow measurements in other external monitoring systems (Zierler, 1965) such as MRI (Ostergaard et al., 1996b;Newman et al., 2003). We previously adapted indicator dilution theory for ophthalmic DyC-OCT . ...
Article
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Studies of flow-metabolism coupling often presume that microvessel architecture is a surrogate for blood flow. To test this assumption, we introduce an in vivo Dynamic Contrast Optical Coherence Tomography (DyC-OCT) method to quantify layer-resolved microvascular blood flow and volume across the full depth of the mouse neocortex, where the angioarchitecture has been previously described. First, we cross-validate average DyC-OCT cortical flow against conventional Doppler OCT flow. Next, with laminar DyC-OCT, we discover that layer 4 consistently exhibits the highest microvascular blood flow, approximately two-fold higher than the outer cortical layers. While flow differences between layers are well-explained by microvascular volume and density, flow differences between subjects are better explained by transit time. Finally, from layer-resolved tracer enhancement, we also infer that microvascular hematocrit increases in deep cortical layers, consistent with predictions of plasma skimming. Altogether, our results show that while the cortical blood supply derives mainly from the pial surface, laminar hemodynamics ensure that the energetic needs of individual cortical layers are met. The laminar trends reported here provide data that links predictions based on the cortical angioarchitecture to cerebrovascular physiology in vivo.
... The computation of relative CBV, CBF, and MTT using DSC-MRI relies on the principles of tracer dilution theory [139,140]. As indicated above, CBV is the most widely used DSC-MRI parameter for brain tumor evaluation and can be estimated using the integral of the ∆R 2 * time profiles in each voxel. ...
... This study used the nominal HCT for the BTEX modeling, which is equivalent to assuming that the myocardium capillary HCT is the same as AIF blood. This simplifying assumption was used in previous publications 6,9,11,74 and also adopted here. The HCT of the capillary blood can be 63-75% of HCT in large vessels 75,76 and difficult to measure in vivo. ...
Article
Purpose: Quantitative myocardial perfusion mapping has advantages over qualitative assessment, including the ability to detect global flow reduction. However, it is not clinically available and remains a research tool. Building upon the previously described imaging sequence, this study presents algorithm and implementation of an automated solution for inline perfusion flow mapping with step by step performance characterization. Methods: Proposed workflow consists of motion correction (MOCO), arterial input function blood detection, intensity to gadolinium concentration conversion, and pixel-wise mapping. A distributed kinetics model, blood-tissue exchange model, is implemented, computing pixel-wise maps of myocardial blood flow (mL/min/g), permeability-surface-area product (mL/min/g), blood volume (mL/g), and interstitial volume (mL/g). Results: Thirty healthy subjects (11 men; 26.4 ± 10.4 years) were recruited and underwent adenosine stress perfusion cardiovascular MR. Mean MOCO quality score was 3.6 ± 0.4 for stress and 3.7 ± 0.4 for rest. Myocardial Dice similarity coefficients after MOCO were significantly improved (P < 1e-6), 0.87 ± 0.05 for stress and 0.86 ± 0.06 for rest. Arterial input function peak gadolinium concentration was 4.4 ± 1.3 mmol/L at stress and 5.2 ± 1.5 mmol/L at rest. Mean myocardial blood flow at stress and rest were 2.82 ± 0.47 mL/min/g and 0.68 ± 0.16 mL/min/g, respectively. The permeability-surface-area product was 1.32 ± 0.26 mL/min/g at stress and 1.09 ± 0.21 mL/min/g at rest (P < 1e-3). Blood volume was 12.0 ± 0.8 mL/100 g at stress and 9.7 ± 1.0 mL/100 g at rest (P < 1e-9), indicating good adenosine vasodilation response. Interstitial volume was 20.8 ± 2.5 mL/100 g at stress and 20.3 ± 2.9 mL/100 g at rest (P = 0.50). Conclusions: An inline perfusion flow mapping workflow is proposed and demonstrated on normal volunteers. Initial evaluation demonstrates this fully automated solution for the respiratory MOCO, arterial input function left ventricle mask detection, and pixel-wise mapping, from free-breathing myocardial perfusion imaging.
... CBF and CBV without any correction were calculated using the standard DSC-MRI theory based on the central volume theorem and Zierler's area-to-height relationship (10)(11)(12): ...
Article
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Dynamic susceptibility contrast magnetic resonance imaging (DSC-MRI) following bolus injection of gadolinium contrast agent (CA) is widely used for the estimation of brain perfusion parameters such as cerebral blood volume (CBV), cerebral blood flow (CBF), and mean transit time (MTT) for both clinical and research purposes. Although it is predicted that DSC-MRI will have superior performance at high magnetic field strengths, to the best of our knowledge, there are no reports of 7 T DSC-MRI in the literature. It is plausible that the transfer of DSC-MRI to 7 T may be accompanied by increased R2∗ relaxivity in tissue and a larger difference in ΔR2∗-versus-concentration relationships between tissue and large vessels. If not accounted for, this will subsequently result in apparent CBV and CBF estimates that are higher than those reported previously at lower field strengths. The aims of this study were therefore to assess the feasibility of 7 T DSC-MRI and to investigate the apparent field-strength dependence of CBV and CBF estimates. In total, 8 healthy volunteers were examined using DSC-MRI at 7 T. A reduced CA dose of 0.05 mmol/kg was administered to decrease susceptibility artifacts. CBV, CBF, and MTT maps were calculated using standard DSC-MRI tracer-kinetic theory. Subject-specific arterial partial volume correction factors were obtained using a tail-scaling approach. Compared with literature values obtained using the tail-scaling approach at 1.5 T and 3 T, the CBV and CBF values of the present study were found to be further overestimated. This observation is potentially related to an inferred field-strength dependence of transverse relaxivities, although issues related to the CA dose must also be considered.
... The implemented BTEX model and other distributed models [11] This study used the nominal HCT for the BTEX modelling, which is equivalent to assuming that the myocardium capillary HCT is the same as AIF blood. This simplifying assumption was used in previous publications [6,9,11,74] and also adopted here. The hematocrit of the capillary blood can be 63%-75% of HCT in large vessels [75,76] and difficult to measure in-vivo. ...
Preprint
Quantitative myocardial perfusion mapping has advantages over qualitative assessment, including the ability to detect global flow reduction. However, it is not clinically available and remains as a research tool. Building upon the previously described imaging sequence, this paper presents algorithm and implementation of an automated solution for inline perfusion flow mapping with step by step performance characterization. An inline perfusion flow mapping workflow is proposed and demonstrated on normal volunteers. Initial evaluation demonstrates the fully automated proposed solution for the respiratory motion correction, AIF LV mask detection and pixel-wise mapping, from free-breathing myocardial perfusion imaging.
... where * indicates the convolution operator and R(t) represents the amount of ICG in brain following an idealized bolus injection of unit concentration (29). The flow-scaled R(t) was determined by deconvolution (21) and its initial height is equal to CBF as R (t = 0) = 1. ...
Article
Background: Post-hemorrhagic ventricular dilatation (PHVD) is predictive of mortality and morbidity among very low birth-weight preterm infants. Impaired cerebral blood flow (CBF) due to elevated intracranial pressure (ICP) is believed to be a contributing factor. Methods: A hyperspectral near-infrared spectroscopy (NIRS) method of measuring CBF and the cerebral metabolic rate of oxygen (CMRO2) was used to investigate perfusion and metabolism changes in patients receiving a ventricular tap (VT) based on clinical management. To improve measurement accuracy, the spectral analysis was modified to account for compression of the cortical mantle caused by PHVD and the possible presence of blood breakdown products. Results: From 9 patients (27 VTs), a significant CBF increase was measured (15.6%) following VT (14.6±4.2 to 16.9±6.6 ml/100 g/min), but with no corresponding change in CMRO2 (1.02±0.41 ml O2/100 g/min). Post-VT CBF was in good agreement with a control group of 13 patients with patent ductus arteriosus but no major cerebral pathology (16.5±7.7 ml/100 g/min), while tissue oxygen saturation (StO2) was significantly lower (58.9±12.1 vs. 70.5±9.1% for controls). Conclusion: CBF was impeded in PHVD infants requiring a clinical intervention, but the effect is not large enough to alter CMRO2.Pediatric Research accepted article preview online, 29 May 2017. doi:10.1038/pr.2017.131.
... Assuming that ΔR 2 * is proportional to contrast agent concentration, we effectively now have a dynamic measure of the amount of contrast agent present in each image voxel. Using the principles of tracer kinetics for nondiffusible tracers [69][70][71] and assuming an intact blood-brain barrier (BBB), the contrast agent concentration in each voxel (C VOI ) can be expressed as ...
... The model used for perfusion quantification in DSC-MRI is based on the principles of tracer kinetics for non-diffusable tracers (Zierler, 1962;Zierler, 1965;Axel, 1980), and relies on the assumption that, in the presence of an intact BBB, the contrast material remains intravascular. ...
Thesis
Two MRI techniques, namely diffusion and perfusion imaging, are becoming increasingly used for evaluation of the pathophysiology of stroke. This work describes the use of these techniques, together with more conventional MRI modalities (such as T1, and T2 imaging) in the investigation of cerebral ischaemia. The work was performed both in a paediatric population in a whole-body clinical MR system (1.5 T) and in an animal model of focal ischaemia at high magnetic field strength (8.5 T). For the paediatric studies, a single shot echo planar imaging (EPI) sequence was developed to enable the on-line calculation of maps of the trace of the diffusion tensor. In the process of this development, it was necessary to address two different imaging artefacts in these maps: eddy current induced image shifts, and residual Nyquist ghost artefacts. Perfusion imaging was implemented using an EPI sequence to follow the passage through the brain of a bolus of a paramagnetic contrast agent. Computer simulations were performed to evaluate the limitations of this technique in the quantification of cerebral blood flow when delay in the arrival and dispersion of the bolus of contrast agent are not accounted for. These MRI techniques were applied to paediatric patients to identify acute ischaemic events, as well as to differentiate between multiple acute events, or between acute and chronic events. Furthermore, the diffusion and perfusion findings were shown to contribute significantly to the management of patients with high risk of stroke, and in the evaluation of treatment outcome. In the animal experiments, permanent middle cerebral artery occlusion was performed in rats to investigate longitudinally the acute MRI changes (first 4-6 hours) following an ischaemic event. This longitudinal analysis contributed to the understanding of the evolution of the ischaemic lesion. Furthermore, the findings allowed the acute identification of tissue 'at risk' of infarction.
... MTT reflects the average time for the blood to pass through a given region of brain tissue, and it is calculated by dividing the CBV by the CBF or using the Zierler area-toheight relationship. 60,61 The MTT is measured in seconds, and the reverse MTT reflects the local cerebral perfusion pressure. 30 MTT removes the need for obtaining absolute values of CBF and CBV; therefore, MTT has the potential to serve as a marker of hemodynamic change in white matter diseases. ...
Article
Background and purpose: White matter lesions of presumed ischemic origin are associated with progressive cognitive impairment and impaired BBB function. Studying the longitudinal effects of white matter lesion biomarkers that measure changes in perfusion and BBB patency within white matter lesions is required for long-term studies of lesion progression. We studied perfusion and BBB disruption within white matter lesions in asymptomatic subjects. Materials and methods: Anatomic imaging was followed by consecutive dynamic contrast-enhanced and DSC imaging. White matter lesions in 21 asymptomatic individuals were determined using a Subject-Specific Sparse Dictionary Learning algorithm with manual correction. Perfusion-related parameters including CBF, MTT, the BBB leakage parameter, and volume transfer constant were determined. Results: MTT was significantly prolonged (7.88 [SD, 1.03] seconds) within white matter lesions compared with normal-appearing white (7.29 [SD, 1.14] seconds) and gray matter (6.67 [SD, 1.35] seconds). The volume transfer constant, measured by dynamic contrast-enhanced imaging, was significantly elevated (0.013 [SD, 0.017] minutes-1) in white matter lesions compared with normal-appearing white matter (0.007 [SD, 0.011] minutes-1). BBB disruption within white matter lesions was detected relative to normal white and gray matter using the DSC-BBB leakage parameter method so that increasing BBB disruption correlated with increasing white matter lesion volume (Spearman correlation coefficient = 0.44; P < .046). Conclusions: A dual-contrast-injection MR imaging protocol combined with a 3D automated segmentation analysis pipeline was used to assess BBB disruption in white matter lesions on the basis of quantitative perfusion measures including the volume transfer constant (dynamic contrast-enhanced imaging), the BBB leakage parameter (DSC), and MTT (DSC). This protocol was able to detect early pathologic changes in otherwise healthy individuals.
... Hence, L 0 represents the transit time of oxygen per unit distance. Moreover, the first derivative of transit time versus time is equal to 1 − H(t), where H(t) is the cumulative frequency function of transit time and represents the fraction of oxygen transmission 36,39 . R 0 represents the fraction of the remaining oxygen convection per unit distance. ...
Article
Full-text available
The oxygen content in the arterial system plays a significant role in determining the physiological status of a human body. Understanding the oxygen concentration distribution in the arterial system is beneficial for the prevention and intervention of vascular disease. However, the oxygen concentration in the arteries could not be noninvasively monitored in clinical research. Although the oxygen concentration distribution in a vessel could be obtained from a three-dimensional (3D) numerical simulation of blood flow coupled with oxygen transport, a 3D numerical simulation of the systemic arterial tree is complicated and requires considerable computational resources and time. However, the lumped parameter model of oxygen transport derived from transmission line equations of oxygen transport requires fewer computational resources and less time to numerically predict the oxygen concentration distribution in the systemic arterial tree. In this study, transmission line equations of oxygen transport are developed according to the theory of oxygen transport in the vessel, and fluid transmission line equations are used as the theoretical reference for the development. The transmission line equations of oxygen transport could also be regarded as the theoretical basis for developing lumped parameter models of other substances in blood.
... The model used for perfusion quantification uses basic principles of tracer kinetics [239,238,6 ] for non-diffusible tracers. The central assumption is th a t the tracer remains intravascular. ...
Thesis
Perfusion is a fundamental biological function, giving an indication of tissue metabolism, through the rate of blood supply. Changes in perfusion accompany almost all forms of brain disease giving a wide range of potential applications for perfusion imaging. Arterial spin labelled MRI, the subject of this thesis, is a good method of measuring brain perfusion. Issues of perfusion quantification, i.e. accuracy and precision are addressed. Current models of the perfusing system assume that water is freely diffusible across the capillary wall. Several published values show that this is not true in the brain where the blood brain barrier restricts water passage. A corrected two-compartment model is presented, with simplifications for use in vivo. Simulations show that the change to perfusion estimation is large. In vivo modelling shows an improved fit for all extremes of perfusion. Perfusion reproducibility is measured for different tissue volumes and is found to compare favourably with other perfusion techniques. A study of thirty-two normal volunteers shows that inter-subject perfusion variation is large, but perfusion within a single subject remains fairly stable over the course of a day and a week. A significant (p<0.05) negative correlation of grey matter perfusion with age is reported, giving a perfusion decrease of 0.5% per year. Female whole brain perfusion is found to be 16% higher than in males (p=0.02). Measurements of perfusion change are made in stroke, arteriovenous malformation (AVM), motor activation and multiple sclerosis. The examples in stroke and motor activation serve as important validation of the technique and the modelling. Gross perfusion abnormalities are detected in AVM showing different perfusion characteristics in different regions of AVM. More subtle changes are found in multiple sclerosis, with significant perfusion increases in the normal appearing white matter compared to normal controls.
Article
A new differential direct curve fit method developed to analyse gas clearance curve is described. It allows rapid tissue blood flow assessment obtained from total or partial tissue desaturation kinetic, without taking into account the base line.
Article
The clinical and angiographic findings in cases of juvenile Moyamoya disease were reviewed and functional images of cerebral perfusion were observed to clarify the mechanism of transient ischemic attack (TIA) which is the characteristic symptom of this disease. A total of fifty two patients with Moyamoya disease were seen in our hospital between 1963 and 1980. Twenty seven were pediatric patients and twenty five were adults. TIA was observed in nineteen of the twenty seven pediatric cases. In thirteen of these nineteen children, TIA was precipitated by physical exercise or emotional upsets such as running, crying or hyperventilation during EEG recording. Angiograms revealed no correlations among the clinical symptoms, the development of the cerebral basal rete, and the degree of the stenosis of the carotid artery. However, the arterial vascularity of the Sylvian group was reduced on the side related to TIA. In seven of the pediatric patients with TIA, cerebral perfusion images were observed during continuous intracarotid infusion of the solution of Kr-81m. The patients were hyperventilated under infusion of the tracer and the changes in cerebral perfusion were detected by a gamma camera. Prolonged and marked reduction of cerebral perfusion was observed in the fronto-pareital convexity region during and after hyperventilation in six of seven patients. This prolonged reduction of perfusion in the fronto-parietal region seems to be responsible for TIA which often occurred following hyperventilation or strenuous exercise.
Article
Regional cerebral blood flow was measured with 133Xe injected into the internal carotid artery in 23 cases of brain tumor and 6 cases of the control. Based on Stochastic method and compartmental method, mean regional cerebral blood flow measured 46±4 ml/100g/min and a model curve was induced from control cases as yy=2294 exp(-0.1153t)±706 exp(-0.019t). Deviation value of each curve from the model curve was analysed as an index for rCBF of tumor and non-tumor area. Regional cerebral blood flow on the tumor consisted of not only one compartment but also two compartments that abnormal high blood flow of arterio-venous channel accompanied with abnormal low blood flow or ordinary cerebral blood flow, namely intratumoral steal flow existed. On the other hand, patterns of cerebral blood flow were simple on non-tumor areas; high or low blood flow, however, inter-regional inhomogeneity of rCBF was demonstrated as follows. According to rCBF on tumor, three groups were classified to high blood flow group (3 cases of glioblastoma, 2 cases of meningioma, 2 cases of astrocytoma and 2 cases of AVM), low blood flow group (2 cases of glioblastoma, 2 cases of meingioma, 2 cases of metastatic tumor and 3 cases of intracerebral hematoma), and normal blood flow group (each case of glioblastoma, meningioma and AVM). Mean rCBF was 36±8 ml/100g/min on non-tumor areas: Perifocal area measured 37±9ml/100g/min and remote area from the tumor measured 36±7 ml/100g/min. No difference of mean rCBF between perifocal and remote area presented. However, 10 cases showed relative perifocal hyperemia that rCBF on perifocal area was higher than on remote area. Eight cases showed relative perifocal ischemia that vis-à-vis. Five cases showed no difference between non-tumor areas. In comparison of rCBF on tumor and non-tumor areas, relative focal hyperemia was demonstrated in 16 cases, relative focal ischemia in 4 cases, and relative focal isoremia in 3 cases. While 10 cases out of the 16 cases associated with relative perifocal hyperemia, all out of the 4 cases associated with relative perifocal ischemia. On another point of view, 6 cases out of 10 cases of relative perifocal hyperemia presented high blood flow on the tumor area and 7 cases out of 8 cases of relative perifocal ischemia presented low blood flow on the tumor area. Cerebral blood flow dynamics of brain tumor was basically characterized into two patterns: 1) In cases of high blood flow on the tumor area, rCBF on the non-tumor areas centrofugally decreased according to the distance from the tumor, that may be called intracerebral steal flow. 2) In cases of low blood flow on the tumor areas, centrofugal increase in rCBF on non-tumor areas that may be functioned as pressure difference in the hemisphere due to brain edema.
Article
Eight children under 15 years of age and 8 adults with basal cerebral rete (so called Moyamoya disease) were examined. Regional cerebral blood flow (rCBF) was measured in 12 of these patients under normocapneic, hypercapneic, hypocapneic and hypotensive states by a ¹³³Xe-intracarotid injection method using a gamma camera. Patients with neurological deficits due to completed stroke (CS) had angiographically poor normograde vascularization of cortical branches of the middle cerebral artery (MCA) and poorly developed collateral circulation. Hemispheric cerebral blood flow (HCBF) in the resting state tended to decrease according to the severity of neurological deficits, but was within the normal range in patients with no neurological deficits. However, focal reduction of rCBF was seen in half of the patients with transient ischemic attacks. Development of leptomeningeal anastomosis of MCA territories from the posterior cerebral artery seemed to have a more important role than basal rete in maintaining cerebral blood flow. There was a significant reduction of the HCBF under the hypocaneic state, but no significant increase under the hypercapneic state. The lack of a CBF response to increased arterial CO2 tension seemed to be due to maximum dilatation of cerebral arterioles.
Thesis
Full-text available
The magnetic resonance imaging (MRI) scanner is a remarkable medical imaging device, capable of producing detailed images of the inside of the body. In addition to imaging internal tissue structures, the scanner can also be used to measure various properties of the tissue. If a tissue property is measured in every image pixel, the resulting property image (the parameter map) can be displayed and used for medical interpretation — a concept referred to as ‘quantitative MRI’. Tissue properties that are commonly probed include traditional MR parameters such as T1, T2 and proton density, as well as functional parameters such as tissue perfusion, brain activation, diffusion and flow. Quantitative MRI relies on the continuous development of new and improved ways to acquire data with the scanner (pulse sequences), to model and analyze the data (postprocessing), and to interpret the output from a medical perspective. This thesis describes methods that have been developed with the specific aim to improve certain quantitative MRI techniques. In particular, the work is focused on improved analysis of perfusion MRI data, and ways to handle the partial volume issue. Constant delivery of oxygen and nutrients via the blood is vital for tissue viability. Perfusion MRI is designed to measure the properties of the local blood delivery, and perfusion images can be used as a marker for tissue health. Whereas rough estimates of perfusion properties can suffice in some cases, more accurate information can provide improved medical research and diagnostics. Most of the methods described in this work aim to provide tissue perfusion information with higher accuracy than previous approaches. One particular way to improve perfusion information is to account for the so-called partial volume effect. This means that limited image resolution implies that a single pixel may contain signal from more than one type of tissue. In other words, the signal can be mixed, and the calculated perfusion represents a mixture of the underlying perfusion of the different tissue types. By first using another quantitative MRI method that estimates the partial volume of each tissue type in every pixel (referred to as partial volume mapping), the partial volume effect can be corrected for by so-called partial volume correction. Partial volume mapping also relates to the field of MRI segmentation, that is, methods to segment an image into different tissue types and anatomical regions. This work also explores and expands a new partial volume mapping and segmentation method, referred to as fractional signal modeling, which seems to be exceptionally versatile and robust, as well as simple to implement and use. A general framework is laid out, with the hope of inspiring more researchers to adapt it and assess its value in different applications. In conclusion, this work improved the quantification in different perfusion MRI methods, as well as presented a new partial volume mapping method. The described methods will hopefully yield value in medical applications in the future.
Article
A new deconvolution technique is described. It regards the Rutland-Patlak plot as the integral of the retention function, and performs deconvolution by creating and then differentiating the Rutland-Patlak plot. The reasoning behind this approach is that in producing the Rutland-Patlak plot, both the content function and the integral of the input function are divided by the input function (i.e. the blood curve), and that this has the effect of producing data equivalent to that which would be produced if the input function did not vary (i.e. if there were a constant blood level of tracer). The concept was tested against data created by modelling techniques. It was able to reproduce retention functions with a variety of different shapes that were used to produce the artificial renogram data. The new deconvolution method is sufficiently simple to be used in either a database or a spreadsheet and does not require any special program units to be written. It does not appear to make any assumptions about the data nor the shape of the retention function, and does not appear to be vulnerable to the oscillating errors that sometimes occur in iterative deconvolution.
Chapter
The circulation of the brain and spinal cord is of interest to those who deal with both the theoretical and practical aspects of neurochemistry, and to neurologists and neurosurgeons, the subject is of crucial interest. This is because a number of clinical conditions are primary disorders of circulation, and many others are complicated by decreases in nutritional blood flow. As a result of this, continuous efforts have been made to devise suitable techniques for measuring CBF in both experimental animals and man. In many applications, one main purpose has been to use CBF data for deriving the cerebral metabolic rate for oxygen (CMR02) and/or glucose (CMRgl).
Conference Paper
Dynamic contrast-enhanced computed tomography (DCE-CT) is an emerging radiological technique, which consists in acquiring a rapid sequence of CT images, shortly after the injection of an intravenous contrast agent. The passage of the contrast agent in a tissue results in a varying CT intensity over time, recorded in time-attenuation curves (TACs), which can be related to the contrast supplied to that tissue via the supplying artery to estimate the local perfusion and permeability characteristics. The time delay between the arrival of the contrast bolus in the feeding artery and the tissue of interest, called the bolus arrival time (BAT), needs to be determined accurately to enable reliable perfusion analysis. Its automated identification is however highly sensitive to noise. We propose an accurate and efficient method for estimating the BAT from DCE-CT images. The method relies on a piecewise linear TAC model with four segments and suitable parameter constraints for limiting the range of possible values. The model is fitted to the acquired TACs in a multiresolution fashion using an iterative optimization approach. The performance of the method was evaluated on simulated and real perfusion data of lung and rectum tumours. In both cases, the method was found to be stable, leading to average accuracies in the order of the temporal resolution of the dynamic sequence. For reasonable levels of noise, the results were found to be comparable to those obtained using a previously proposed method, employing a full search algorithm, but requiring an order of magnitude more computation time. © (2017) COPYRIGHT Society of Photo-Optical Instrumentation Engineers (SPIE). Downloading of the abstract is permitted for personal use only.
Chapter
IntroductionFrequency of different pathological types of strokeDifferentiating ischaemic stroke from intracerebral haemorrhageCT scanningMagnetic resonance imagingOther ‘sophisticated’ methods of imaging cerebral ischaemiaDifferentiating haemorrhagic transformation of an infarct from intracerebral haemorrhageImaging of intracranial venous thrombosis
Article
Dynamic contrast‐enhanced magnetic resonance imaging (DCE‐MRI) is a promising approach to assess microvascular blood flow (perfusion) within the myocardium, and the Fermi microvascular perfusion model is widely applied to extract estimates of the myocardial blood flow (MBF) from DCE‐MRI data sets. The classification of myocardial tissues into normal (healthy) and hypoperfused (lesion) regions provides new opportunities for the diagnosis of coronary heart disease and for advancing our understanding of the aetiology of this highly prevalent disease. In the present paper, the Fermi model is combined with a hierarchical Bayesian model (HBM) and a Markov random fields prior to automate this classification. The proposed model exploits spatial context information to smooth the MBF estimates while sharpening the edges between lesions and healthy tissues. The model parameters are approximately sampled from the posterior distribution with Markov chain Monte Carlo (MCMC), and we demonstrate that this enables robust classification of myocardial tissue elements based on estimated MBF, along with sound uncertainty quantification. A well‐established traditional method, based on a Gaussian mixture model (GMM) trained with the expectation–maximisation algorithm, is used as a benchmark for comparison.
Article
Purpose Systematic differences with respect to myocardial perfusion quantification exist between DCE‐MRI and PET. Using the potential of integrated PET/MRI, this study was conceived to compare perfusion quantification on the basis of simultaneously acquired ¹³NH3‐ammonia PET and DCE‐MRI data in patients at rest and stress. Methods Twenty‐nine patients were examined on a 3T PET/MRI scanner. DCE‐MRI was implemented in dual‐sequence design and additional T1 mapping for signal normalization. Four different deconvolution methods including a modified version of the Fermi technique were compared against ¹³NH3‐ammonia results. Results Cohort‐average flow comparison yielded higher resting flows for DCE‐MRI than for PET and, therefore, significantly lower DCE‐MRI perfusion ratios under the common assumption of equal arterial and tissue hematocrit. Absolute flow values were strongly correlated in both slice‐average (R² = 0.82) and regional (R² = 0.7) evaluations. Different DCE‐MRI deconvolution methods yielded similar flow result with exception of an unconstrained Fermi method exhibiting outliers at high flows when compared with PET. Conclusion Thresholds for Ischemia classification may not be directly tradable between PET and MRI flow values. Differences in perfusion ratios between PET and DCE‐MRI may be lifted by using stress/rest‐specific hematocrit conversion. Proper physiological constraints are advised in model‐constrained deconvolution.
Chapter
Magnetic resonance imaging (MRI) enables non-invasive in vivo imaging with excellent contrast between different types of soft tissue. One of the strengths of MRI is the variety of contrasts that it is able to provide. Traditionally, MRI images have been acquired with contrast based on tissue type and macrostructure, allowing detailed depiction of anatomy. More recently, complementary methods have been developed which derive their contrasts from tissue microstructure (at the level of the cells) and physiology (oxygen utilisation and blood perfusion). In this chapter, the most widely-used MR methods for imaging the brain will be described, and the mechanisms responsible for the sensitivity of these methods to pathophysiology in brain disease will be explained. © Springer International Publishing AG, part of Springer Nature 2018.
Chapter
This chapter outlines general considerations on magnetic resonance safety. Cardiac magnetic resonance spectroscopy substantially preceded the development of cardiac magnetic resonance (CMR). Magnetic resonance imaging (MRI) views the water and fat in the human body by observing the hydrogen nuclei in these molecules. The most important feature of the CMR scanner is the magnet. These magnets are kept permanently at magnetic field. Careful preparation of the patient is necessary in order to maximize diagnostic information from the CMR scan. Cardiac anatomy can easily be demonstrated using MRI techniques, which are not confined to the three orthogonal planes as in conventional imaging. CMR has rapidly become the imaging method of choice and the gold standard in the assessment of cardiac function of both normal and abnormal ventricles. The ability of CMR to image in any plane without the need for optimal imaging windows allows for unprecedented flexibility for the interrogation of abnormal heart structures.
Article
The understanding of microvascular dysfunction without evidence of epicardial coronary artery disease pales in comparison with that of obstructive epicardial coronary artery disease. A primary limitation in the past had been the lack of development of noninvasive methods of detecting and quantifying microvascular dysfunction. This limitation has particularly affected the ability to study the pathophysiology, morbidity, and treatment of this disease. More recently, almost all of the noninvasive cardiac imaging modalities have been used to quantify blood flow and advance understanding of microvascular dysfunction.
Chapter
We have measured RBC velocity profiles for mammalian arterioles and venules from high-speed cinematographic motion pictures. Measurements were made at 320× and 400× optical magnification over an averaging time period of 10 ms. In vivo profiles are uniformly nonsymmetrical, the RBCs exhibit rotation, and they frequently deviate sidewise from the overall axial direction of motion. In general, this is more pronounced on the venous side. Since all of the profiles are time variant and the average values are synchronous with the midstream velocity, individual RBC velocities will vary about the average. Profiles become more blunted in vessels with smaller diameters. In vessels below 16 μm diameter, the velocity gradients between adjacent RBCs are quite small; for large vessels, recognizable profiles develop and become fully developed in blood vessels above 30 μm in diameter. This blunting is further affected by the midstream velocity and the local hematocrit; when the velocity is reduced below 1.2 mmls and/or an increased hematocrit is present, the profile becomes more blunted.
Thesis
Measurements of cerebral perfusion are increasingly made using magnetic resonance techniques. The two main MR approaches to perfusion measurement are bolus tracking and arterial spin labelling (ASL), and aspects of both are investigated in the research described in this thesis. Bolus tracking within the adult patient population is becoming common, but its use in young children has so far been relatively limited. Data collected in normal children less than 30 months old are used to assess the reliability and age dependence of perfusion measurements in early childhood. Deconvolution is generally regarded to be the most robust approach to the analysis of bolus tracking data. However, current deconvolution techniques are inappropriate in cases of severe cerebrovascular disease, and an alternative is the use of 'summary parameters' as indicators of tissue perfusion status. These parameters have many theoretical drawbacks, and the reliability of their use is investigated using numerical simulations. ASL techniques are advantageous in that they require no exogenous contrast agents, thus facilitating repeated measurements, and perfusion can potentially be quantified in absolute units. However, the size of the perfusion-related signal means that ASL sequence implementation is not straightforward. The implementation of the FAIR ASL technique at our institution is described, including a discussion of the problems encountered. Current ASL techniques suffer from many inherent problems, including low signal-to- noise ratio and sensitivity to arterial transit times. A new sequence, designed to ameliorate some of these issues, is proposed and implemented. The novel sequence is investigated in vivo, and through numerical simulation. Comparison with a standard ASL technique showed that the novel sequence does lead to improved signal-to-noise ratio and reduced transit times. However, significant problems with the sequence remain to be resolved, and potential solutions to these are described and discussed.
Chapter
Perfusion refers to the biological process of blood flow through vascularized tissue and allows for sufficient delivery of vital nutrients to most organs in the body as well as removal of metabolic waste and heat. Thus, perfusion plays a critical role in determining physiological levels of oxygenation, bioenergetics status, and pH distributions. Neoplasms in the brain, including brain tumors, are typically characterized by irregular and insufficient perfusion from abnormal neo-vasculature. Consequently, brain tumors create a hostile microenvironment that promotes tumor aggressiveness and treatment resistance. Moreover, treatment-induced changes in physiological functions, such as perfusion, may occur rapidly and before any measurable reduction in tumor volume. Hence, spatial and temporal assessment of quantitative perfusion metrics is an ideal target for diagnosis and treatment response monitoring of brain tumors. While conventional magnetic resonance imaging (MRI) remains the gold standard for non-invasive characterization of tumors of the central nervous system (CNS), quantitative measures of perfusion by dynamic susceptibility contrast (DSC)-MRI and arterial spin labeling (ASL) have helped advance cancer imaging as a non-invasive diagnostic force in the fight against cancer. Here, we review DSC-MRI and ASL, and their current and potential use in the clinical management of brain tumors.
Article
Full-text available
Background: FMRI signal amplitude can change during stimulus presentation due to underlying neural function and hemodynamic responses limiting the accuracy of fMRI in pre-surgical planning. To account for these changes in fMRI activation signal, we used breath-hold tasks to mimic hemodynamic changes in brain tumor subjects and scaled the activation response. Methods: Motor and/or language fMRI was performed in 21 subjects with brain tumor. A breath-hold task was also performed in these subjects to obtain the hemodynamic response changes independent of neural changes. The task activation signals were calibrated on a voxel wise basis for all the subjects. Direct cortical stimulation was used to verify the scaled results of task-based fMRI. Results: After scaling for the hemodynamic response function (HRF) on a voxel wise basis, the spatial extent of the scaled activation was more clustered together and appeared to minimize false positives. Similarly, accounting for the underlying canonical HRF, the percentage increase of active voxels after scaling had lower standard non-deviation suggesting that the activation response across voxels were more similar. Conclusion: Although preliminary in nature, this study suggests that the variation in hemodynamic changes can be calibrated using breath-hold in brain tumor subjects and can also be used for other clinical cases where the underlying HRF has been altered.
Thesis
Es wurden Perfusionsmessungen mittels MRT an Infarktpatienten im Akutstadium und im Langzeitverlauf durchgeführt und quantitativ mittels einem Sektormodell ausgewertet. Hierbei zeigte sich, dass sich die Perfusionswerte im Infarktareal und gesunden Myokard nicht signifikant unterschieden und dass sich diese auch im Jahresverlauf nicht signifikant änderten. Es ergab sich auch keine signifikante Korrelation zwischen der Größe des Infarkareales und den gemessenen Perfusionswerten.
pMR imaging is a useful examination that can be performed easily, safely, and inexpensively in the evaluation of cerebrovascular disease in the pediatric patient. Postprocessed perfusion images offer valuable information for characterizing perfusion abnormalities. Parametric images of rCBV and rCBF seem to yield the highest diagnostic specificity, but the best format for representations of pMR imaging data is likely to be influenced by the experience of the neuroradiologist and will vary with the pathology of interest. Because of their high specificity for cerebrovascular disease but low sensitivity, pMR images should be interpreted only in conjunction with conventional anatomical MR imaging for evaluating cerebrovascular disease in children. The authors have found the accuracy in the interpretation of all pMR imaging formats to improve dramatically with experience. Further long-term studies using echo-planar perfusion imaging are necessary to evaluate its impact on the sensitivity and specificity of pMR images in the evaluation of cerebrovascular disease. Although pMR images offer improved specificity for diagnosing cerebrovascular disease in children, the impact on patient management also will require further evaluation.
Article
Full-text available
Cardiac magnetic resonance myocardial perfusion imaging can detect coronary artery disease and is an alternative to single-photon emission computed tomography or positron emission tomography. However, the complex, non-linear MR signal and the lack of robust quantification of myocardial blood flow have hindered its widespread clinical application thus far. Recently, a new Bayesian approach was developed for brain imaging and evaluation of perfusion indexes (Kudo et al., 2014). In addition to providing accurate perfusion measurements, this probabilistic approach appears more robust than previous approaches, particularly due to its insensitivity to bolus arrival delays. We assessed the performance of this approach against a well-known and commonly deployed model-independent method based on the Fermi function for cardiac magnetic resonance myocardial perfusion imaging. The methods were first evaluated for accuracy and precision using a digital phantom to test them against the ground truth; next, they were applied in a group of coronary artery disease patients. The Bayesian method can be considered an appropriate model-independent method with which to estimate myocardial blood flow and delays. The digital phantom comprised a set of synthetic time-concentration curve combinations generated with a 2-compartment exchange model and a realistic combination of perfusion indexes, arterial input dynamics, noise and delays collected from the clinical dataset. The myocardial blood flow values estimated with the two methods showed an excellent correlation coefficient (r2 > 0.9) under all noise and delay conditions. The Bayesian approach showed excellent robustness to bolus arrival delays, with a similar performance to Fermi modeling when delays were considered. Delays were better estimated with the Bayesian approach than with Fermi modeling. An in vivo analysis of coronary artery disease patients revealed that the Bayesian approach had an excellent ability to distinguish between abnormal and normal myocardium. The Bayesian approach was able to discriminate not only flows but also delays with increased sensitivity by offering a clearly enlarged range of distribution for the physiologic parameters.
Article
A new method for determining regional blood flow in tissue by means of the inert radioactive gas Krypton85 is presented. The method has been applied on the exposed cerebral cortex of anesthetized rabbits, cats and dogs. The radioisotope Kr85, a weak beta emitter, was dissolved in saline which was then injected into the carotid artery of the hemisphere to be studied. The rapid uptake and slower clearance of the isotope was recorded from a small area of the exposed cortical surface, about 1 mm in depth. The theory of analyzing the clearance curves and of calculating the average regional cortical blood flow in ml per gram per minute is described. The method requires constant blood flow in the tissue during the measurement (about 5 min). It may, however, to some extent be used for studies of acute changes in perfusion. It is also possible to use it in a continuous fashion. It has been possible to confirm and to study in quantitative terms the correlation between arterial carbon dioxide tension or cortical functional activity, and the regional cortical blood flow. The method is simple to use and permits repeated measurements in the same experiment with minimal interference with the functional activity of the brain. The method may readily be adapted for studies in man
Article
1. Human myocardial blood flow has been measured by the determination of precordial radioactivity after the injection of solutions of radioactive gas directly into the coronary arteries following coronary arteriography. 2. The accuracy of radioactive gas measurements has been established in dog experiments by comparison with coronary blood flow simultaneously measured by rotameter. 3. This method has two major advantages over the existing methods of measuring human myocardial blood flow. Firstly, the right and left coronary circulations can be studied separately, this being the only method whereby the right circulation can be studied in man. Secondly, anatomical and physiological correlations are readily available as arteriography is an essential feature of the method.
The measurement of myocardial blood flow in animal and man by selective injection of radioactive inert gas into the coronary artery
  • R S Ross
  • Ueda K
  • R Lichtlex P
  • R Rees J