Intravascular Volume Fraction Research Articles

Simultaneous assessment of cerebral blood volume and diffusion heterogeneity using hybrid IVIM and DK MR imaging: initial experience with brain tumors

ObjectivesTo investigate the feasibility of simultaneously assessing cerebral blood volume and diffusion heterogeneity using hybrid diffusion-kurtosis (DK) and intravoxel-incoherent-motion (IVIM) MR imaging.MethodsFifteen healthy volunteers and 30 patients with histologically proven brain tumours (25 WHO grade II–IV gliomas and five metastases) were recruited. On a 3-T system, diffusion-weighted imaging was performed with six b-values ranging from 0 to 1,700 s/mm2. Nonlinear least-squares fitting was employed to extract diffusion coefficient (D), diffusion kurtosis coefficient (K, a measure of the degree of non-Gaussian and heterogeneous diffusion) and intravascular volume fraction (f, a measure proportional to cerebral blood volume). Repeated-measures multivariate analysis of variance and receiver operating characteristic analysis were performed to assess the ability of D/K/f in differentiating contrast-enhanced tumour from peritumoral oedema and normal-appearing white matter.ResultsBased on our imaging setting (baseline signal-to-noise ratio = 32–128), coefficient of variation was 14–20 % for K, ~6 % for D and 26–44 % for f. The indexes were able to differentiate contrast-enhanced tumour (Wilks’ λ = 0.026, p < 10-3), and performance was greatest with K, followed by f and D.ConclusionsHybrid DK IVIM imaging is capable of simultaneously measuring cerebral perfusion and diffusion indexes that together may improve brain tumour diagnosis.Key Points• Hybrid DK-IVIM imaging allows simultaneous measurement of K, D and f.• Combined K/D/f better demarcates contrast-enhanced tumour than they do separately.• f correlates better with contrast-leakage-corrected CBVDSCthan with uncorrected CBVDSC.

Evaluation of the middle cerebral artery occlusion techniques in the rat by in-vitro 3-dimensional micro- and nano computed tomography

BackgroundAnimal models of focal cerebral ischemia are widely used in stroke research. The purpose of our study was to evaluate and compare the cerebral macro- and microvascular architecture of rats in two different models of permanent middle cerebral artery occlusion using an innovative quantitative micro- and nano-CT imaging technique.Methods4h of middle cerebral artery occlusion was performed in rats using the macrosphere method or the suture technique. After contrast perfusion, brains were isolated and scanned en-bloc using micro-CT (8 μm)3 or nano-CT at 500 nm3 voxel size to generate 3D images of the cerebral vasculature. The arterial vascular volume fraction and gray scale attenuation was determined and the significance of differences in measurements was tested with analysis of variance [ANOVA].ResultsMicro-CT provided quantitative information on vascular morphology. Micro- and nano-CT proved to visualize and differentiate vascular occlusion territories performed in both models of cerebral ischemia. The suture technique leads to a remarkable decrease in the intravascular volume fraction of the middle cerebral artery perfusion territory. Blocking the medial cerebral artery with macrospheres, the vascular volume fraction of the involved hemisphere decreased significantly (p < 0.001), independently of the number of macrospheres, and was comparable to the suture method. We established gray scale measurements by which focal cerebral ischemia could be radiographically categorized (p < 0.001). Nano-CT imaging demonstrates collateral perfusion related to different occluded vessel territories after macrosphere perfusion.ConclusionMicro- and Nano-CT imaging is feasible for analysis and differentiation of different models of focal cerebral ischemia in rats.

Relationship of Skeletal Muscle Perfusion Measured by Contrast-Enhanced Ultrasonography to Histologic Microvascular Density

The purpose of this study was to compare skeletal muscle perfusion measured by contrast-enhanced ultrasonography (CEUS) with microvascular density in muscle biopsies. Power Doppler sonography after intravenous bolus injection of Levovist (SH U 508A; Schering AG, Berlin, Germany) was used to examine perfusion of vastus lateralis muscle in 23 healthy volunteers. Local blood volume (B), blood flow velocity (v), and blood flow (f) were calculated by analyzing replenishment kinetics. CEUS perfusion was compared with vascularization of biopsy samples from vastus lateralis muscle. Subjects were selected such that their aerobic capacity (maximal oxygen uptake [VO(2)max]) per body weight ranged between 23 and 66 mL . min(-1) . kg(-1) to render a large variability of skeletal muscle capillarization. Moreover, subjects' venous blood hematocrit (Hkt) was determined to estimate the plasmatic intravascular volume fraction (1-Hkt=PVF) in which the microbubbles can distribute. Median capillary density was 331/mm(2) (range, 207-469/mm(2)), and median capillary fiber contacts (CFC) were 3.6 (range, 2.3-6.5). CFC was correlated with VO(2)max (r=0.59; P<.01). Among CEUS parameters, B showed the closest correlation to CFC (r=0.53; P<.01). When CFC was normalized for PVF, correlation of B to CFC was r=0.64 (P<.01). CEUS could depict the physiologic large variability of vastus lateralis muscle perfusion at rest (median [range]: B, 2.5 [0.1-12.3] approximately mL; v, 0.3 [0.1-3.7] mm/s; f, 0.7 [0.1-5.3] approximately mL . min(-1) . 100 g tissue(-1)). B is significantly related to fiber-adjacent capillarization and may represent physiologic capillary recruitment (eg, through metabolic fiber-related signals). CEUS is feasible for skeletal muscle perfusion quantification.

Parametric imaging of tumor perfusion using flow- and permeability-limited tracers.

To quantitatively evaluate the spatial distribution of flow- and permeability-limited perfusion in MCF7 human breast cancer tumors orthotopically implanted in CD1-NU mice. Flow-limited perfusion was derived from (2)H-MRI recorded before and after infusion of deuterated water. Permeability-limited perfusion was evaluated from GdDTPA-enhanced (1)H-MRI. The dominant processes in tumor perfusion, namely blood flow and capillary permeability, were mapped in orthotopically implanted MCF7 human breast cancer tumors. The dynamic data were processed according to physiological models, yielding parametric maps of intravascular volume fraction, water perfusion rate, GdDTPA permeability rate constant, and extracellular volume fraction accessible to GdDTPA. The maps exhibited the heterogeneous distribution of each perfusion parameter. Most of the tumor tissue (> or =95%) was perfused with HDO, while GdDTPA was perfused in only about 50% of it. In most loci the perfusion rate was limited by capillary permeability to GdDTPA. The results demonstrated the instructive value of tracers with different properties used in conjunction to achieve a deeper understanding of tumor perfusion capacity. This study offers tools for the accurate, noninvasive evaluation of drug delivery efficacy.

Parametric Imaging of Tumor Perfusion with Deuterium Magnetic Resonance Imaging

Imaging of the vasculature and its functioning over the entire lesion may significantly aid in cancer diagnosis, assessment of prognosis, and therapeutic evaluation. In the current study we present a dynamic three-dimensional deuterium magnetic resonance imaging method that determines the intravascular volume fraction and water perfusion rate at a resolution of 2 mm2/pixel. The method was tested and utilized to characterize the vasculature of orthotopic MCF7 human breast cancer tumors in CD1-NU athymic mice. A new algorithm based on Patlak's kinetic model was developed to analyze the dynamic images acquired during and after termination of infusion with deuterated water. The resulting parametric maps spanned a wide range from 0.4 to 35.2% for the intravascular volume fraction and from 4 × 10−6 to 3.9 × 10−3 min−1 for the perfusion rate and exhibited high intratumoral and intertumoral heterogeneity at both parameters. The intravascular volume fraction did not correlate with the corresponding perfusion rate, demonstrating the irregular outgrowth of tumor neovascularization. Averaging the data or analyzing at spatially degraded resolution completely masked the presence of both “hot spots” and hypoxic loci, highlighting the critical importance of high spatial resolution. The method is applicable to other types of tumors and animal models and may be extended to humans.

Contrast echocardiographic quantification of regional myocardial perfusion: Validation with an isolated rabbit heart model

Quantification of regional myocardial tissue blood flow (RMBF) based on contrast echocardiography has yet to be achieved. This study validated our recently proposed algorithm for quantification of RMBF with colored microspheres. Experiments were carried out in an isolated rabbit heart preparation ( n = 11). Aortic root injections of perfluoropropane-filled albumin microsphere solution (FS069) and colored microspheres were performed at five levels of coronary flow achieved by altering perfusion pressure. During each injection of contrast material, consecutive end-diastolic images of the heart and an extracardiac reference chamber were acquired with a 7.5 MHz transducer and digitized. Time-intensity curves from the reference chamber and myocardial regions of interest, corresponding to the anatomic segments used for colored microsphere analysis, were analyzed for RMBF. Blood flow was calculated as the intravascular volume fraction (ratio of areas under myocardial and reference curves) divided by mean transit time (deconvolution of impulse response) and compared with those obtained with colored microspheres. Injections of FS069 resulted in highly reproducible enhancement of myocardial contrast. Analysis of time-intensity curves provided consistent measurements of RMBF ( r = 0.91), which correlated highly with microsphere data ( r = 0.84). The use of this new algorithm allows accurate quantification of RMBF in the isolated heart model. Further validation of this approach in an animal model with peripheral intravenous injections of contrast material will allow noninvasive clinical measurements of RMBF.

971-55 Can Regional Myocardial Tissue Blood Flow be Measured in Terms of ml/min/g Using Contrast Echocardiography?

Absolute quantification of regional myocardial tissue blood flow (RMBF) based on contrast echocardiography has not yet been achieved. The aim of this study was to validate of our recently proposed algorithm for the quantification of RMBF and examine its reproducibility. This approach evaluates RMBF as the intravascular volume fraction (ratio of the areas under myocardial time intensity curve and a curve obtained from a reference region of interest) divided by mean transit time (obtained using deconvolution of impulse response). Experiments were carried out using an isolated rabbit heart model (N = 8), wherein coronary blood flow was controlled by varying perfusion pressure. Factors confounding in-vivo experimentation, such as cardiac translation and limited image quality, were eliminated in this setup. Aortic root injections of FS069, a new stable contrast solution (MBI, 1:200 in saline, filtered using a 8 /μ-pore filter) and colored microspheres, used as the “gold” standard for reference, were performed at different levels of coronary flow. During contrast injections, end-diastolic images of the heart and an extracardiac reference chamber were acquired using a 7.5 MHz transducer and digitized on-line and processed using the above algorithm. Contrast echocardiographic measurements of RMBF highly correlated with microsphere flow (figure). Bland-Altman analysis revealed an insignificant bias of 0.07 ml/min/gr, with 95% limits of agreement at 0.69 ml/min/g. Using this algorithm, repeated evaluations of RMBF were highly reproducible (r = 0.92). In summary, the use of this new algorithm in conjunction with stable contrast agents, such as FS069, allows accurate and reproducible quantification of RMBF.

Myocardial regional blood flow: Quantitative measurement by computer analysis of contrast enhanced echocardiographic images

Quantitation of regional myocardial blood flow constitutes the missing link between the anatomy of coronary obstruction and its physiological effect on regional oxygen supply. Microscopic air bubbles, introduced into the coronary circulation, were shown to produce a transitory enhancement of the myocardial tissue contrast, easily detectable with standard ultrasonic imaging equipment. This study presents a new approach linking the tissue blood flow with the time-dependent changes in the intensity of the ultrasonic reflections produced by the microbubbles. The tissue blood flow is evaluated using the well-known indicator dilution relation, according to which flow equals the ratio between the intravascular fraction of the tissue sample volume and the mean transit time of the contrast agent. We derive these two parameters from the time curves representing the contrast induced variations in the mean videointensity measured in two regions of interest, a reference region in the left ventricular cavity and the region of interest within the myocardial tissue. The intravascular volume fraction is computed as the ratio of the total power of the above two intensity curves, as each of these is assumed to be proportional to the total amount of tracer traversing the corresponding region of interest. The mean transit time is computed using combined time- and frequency-domain processing, involving Fourier deconvolution of the response function of the myocardial tissue sample. This approach was validated in an in vivo model in a series of animal experiments involving left atrial injection of albumin coated air microbubbles (Albunex®). Videointensity curves obtained during contrast enhancement of the myocardium were analyzed to provide values of regional myocardial blood flow (in mL/min/100 g) in 45 myocardial regions of interest defined in 7 experiments performed on 4 animals. The values obtained with our approach correlated well ( r = 0.77, p < 0.001) with standard reference measurements based on radiolabeled microspheres. The intertechnique variability was found to be smaller than the intersegment variability characterizing our technique. The difference between the mean flow values obtained with microspheres for segments of the entire heart and the mean flow obtained with our technique for all regions of interest ranged between 1 to 19% in the 7 experiments. In its present form, based on left atrial or left ventricular injection of contrast solution, this method may allow, for the first time, quantitative evaluation of myocardial regional blood supply in the cardiac catheterization laboratory or the operation theater. With further development of contrast agents suitable for transpulmonary enhancement of the myocardium by peripheral intravenous injection, this technique may provide the basis for the noninvasive quantitative measurement of myocardial tissue blood flow.

The microvascular system of the optic nerve in control and enucleated rats

The microvascular system of the optic nerve of the rat was examined morphometrically to determine the effect of enucleation of one eye at birth on the microvascular development in the contralateral optic nerve. For this purpose, two groups of rats were used: three were unilaterally enucleated on the day of birth and studied on postnatal Day 28; three littermates were used as controls. Using plastic embedded semithin sections, we analyzed various parameters and compared the results statistically. The average diameter of microvessels up to 7.5 μm was found to be 4.7 ± 0.2 μm in controls and 5.3 ± 0.5 μm in experimental rats. The density of microvessels expressed as the mean number of sectioned capillaries per tissue area was 137 ± 25/mm 2 in the control group and 169 ± 32/mm 2 in the experimental group. The intravascular volume fraction percentage ( V v), which represents the volume fraction of the capillary network per unit of optic nerve volume (mm 3/mm 3%), was 0.06% in the controls and 0.10% in the enucleated rats. Total length of capillaries per unit of volume ( L v) averaged 1050 ± 112 and 2235 ± 195 mm/mm 3 in control and experimental groups, respectively. The internal capillary surface area available for metabolic exchange expressed per volume unit ( S v) was 15.5 ± 2.1 and 37.2 ± 2.8 mm 2/mm 3 in control and experimental groups, respectively. These results, together with the lack of ultrastructural modifications in the vascular walls of microvessels, suggest that these rearrangements of the capillary system in the enucleated group could be triggered by an increase in the optic nerve metabolism resulting from monocular vision.

Morphometric investigation of the microvascular system of pancreatic exocrine and endocrine tissue in the rat

Morphometric data were obtained from the microvasculature in exocrine and endocrine tissue of the rat pancreas. Two groups of anesthetized rats (100 and 300 g body wt, respectively), received intravenous injections of fluorochrome-coupled globulins in order to label the entire vascular system. After circulation of fluorescein-isothiocyanate (FITC)-globulin through the vascular system for 30 min and lissamine rhodamine B 200 (RB 200)-globulin for 5 min, the pancreas was frozen rapidly. In frozen sections of the organ, both dyes showed the same intravascular distribution. The mean number of sectioned vascular elements was 970 ± 40/mm 2 in the exocrine parenchyma and 1430 ± 60/mm 2 in islet tissue. The cross-sectional area fraction of the microvascular system, which is equivalent to the intravascular volume fraction, amounted to 0.027 ± 0.001 mm 2/mm 2 in the exocrine system and to 0.061 ± 0.002 mm 2/mm 2 in the endocrine pancreas. The corresponding values for microvascular surface area (mm 2/mm 3) were 18.0 ± 0.8 (exocrine tissue) and 34.2 ± 2.0 (endocrine tissue). Mean diameters of vessels up to 10 μm in exocrine tissue amounted to 5.5 ± 0.2 and 6.1 ± 0.1 μm in exocrine and endocrine tissues, respectively; when all vessels up to 30 μm in diameter were considered, these values amounted to 5.7 ± 0.2 and 6.7 ± 0.2 μm, respectively. Especially in light of the fact that flow rate was observed to be much higher in islets than in acini, the present results support the existence of an insular microcirculatory system which is specialized in terms of its exchange capacity.