Fractional Vascular Volume Research Articles

Dynamic contrast-enhanced computed tomography in dogs with nasal tumors.

Treatment of nasal tumors in dogs is associated with high morbidity and reliable prognostic factors are lacking. Dynamic contrast-enhanced computed tomography (DCECT) can be used to assess tumor perfusion. To assess perfusion parameters of nasal tumors (correlating with tumor type) before and during radiotherapy (RT) and find potential correlation with survival. Twenty-four client-owned dogs with nasal tumors, including 16 epithelial tumors and 8 sarcomas. Prospective cross-sectional study. All dogs had baseline DCECT to assess fractional vascular volume (BV), blood flow (BF), and transit time (TT). Thirteen dogs had repeat DCECT after 12 Gy of megavoltage RT. Survival times were calculated. Median BV was 17.83 mL/100 g (range, 3.63-66.02), median BF was 122.63 mL/100 g/minute (range, 23.65-279.99), and median TT was 8.91 seconds (range, 4.57-14.23). Sarcomas had a significantly lower BF than adenocarcinomas (P = .002), carcinomas (P = .01), and other carcinomas (P = .001), and significantly lower BV than adenocarcinomas (P = .03) and other carcinomas (P = .004). Significant associations were found between epithelial tumors and sarcoma for change in tumor volume (P = .01), width (P = .004), and length (P = .02) in that epithelial tumors decreased in volume whereas sarcomas increased in volume. Perfusion parameters were not correlated with survival. Nasal sarcomas have lower BV and BF than nasal carcinomas, and sarcomas have a lower size reduction than carcinomas early on during RT. Baseline results and changes in perfusion parameters may not be correlated with survival.

CLARITY for High-resolution Imaging and Quantification of Vasculature in the Whole Mouse Brain.

Elucidating the normal structure and distribution of cerebral vascular system is fundamental for understanding its function. However, studies on visualization and whole-brain quantification of vasculature with cellular resolution are limited. Here, we explored the structure of vasculature at the whole-brain level using the newly developed CLARITY technique. Adult male C57BL/6J mice undergoing transient middle cerebral artery occlusion and Tie2-RFP transgenic mice were used. Whole mouse brains were extracted for CLARITY processing. Immunostaining was performed to label vessels. Customized MATLAB code was used for image processing and quantification. Three-dimensional images were visualized using the Vaa3D software. Our results showed that whole mouse brain became transparent using the CLARITY method. Three-dimensional imaging and visualization of vasculature were achieved at the whole-brain level with a 1-μm voxel resolution. The quantitative results showed that the fractional vascular volume was 0.018 ± 0.004 mm3 per mm3, the normalized vascular length was 0.44 ± 0.04 m per mm3, and the mean diameter of the microvessels was 4.25 ± 0.08 μm. Furthermore, a decrease in the fractional vascular volume and a decrease in the normalized vascular length were found in the penumbra of ischemic mice compared to controls (p < 0.05). In conclusion, CLARITY provides a novel approach for mapping vasculature in the whole mouse brain at cellular resolution. CLARITY-optimized algorithms facilitate the assessment of structural change in vasculature after brain injury.

Development of a mathematical model to estimate intra-tumor oxygen concentrations through multi-parametric imaging.

BackgroundTumor hypoxia is involved in every stage of solid tumor development: formation, progression, metastasis, and apoptosis. Two types of hypoxia exist in tumors—chronic hypoxia and acute hypoxia. Recent studies indicate that the regional hypoxia kinetics is closely linked to metastasis and therapeutic responses, but regional hypoxia kinetics is hard to measure. We propose a novel approach to determine the local pO2 by fusing the parameters obtained from in vivo functional imaging through the use of a modified multivariate Krogh model.MethodsTo test our idea and its potential to translate into an in vivo setting through the use of existing imaging techniques, simulation studies were performed comparing the local partial oxygen pressure (pO2) from the proposed multivariate image fusion model to the referenced pO2 derived by Green’s function, which considers the contribution from every vessel segment of an entire three-dimensional tumor vasculature to profile tumor oxygen with high spatial resolution.ResultspO2 derived from our fusion approach were close to the referenced pO2 with regression slope near 1.0 and an r2 higher than 0.8 if the voxel size (or the spatial resolution set by functional imaging modality) was less than 200 μm. The simulation also showed that the metabolic rate, blood perfusion, and hemoglobin concentration were dominant factors in tissue oxygenation. The impact of the measurement error of functional imaging to the pO2 precision and accuracy was simulated. A Gaussian error function with FWHM equal to 20 % of blood perfusion or fractional vascular volume measurement contributed to average 7 % statistical error in pO2.ConclusionThe simulation results indicate that the fusion of multiple parametric maps through the biophysically derived mathematical models can monitor the intra-tumor spatial variations of hypoxia in tumors with existing imaging methods, and the potential to further investigate different forms of hypoxia, such as chronic and acute hypoxia, in response to cancer therapies.Electronic supplementary materialThe online version of this article (doi:10.1186/s12938-016-0235-5) contains supplementary material, which is available to authorized users.

Gd-loaded-RBCs for the assessment of tumor vascular volume by contrast-enhanced-MRI

The assessment of the fractional vascular volume (vV) in the tumor area is of great interest in the characterization of tumor and it can be useful to monitor the outcome of anti-angiogenetic therapies. The high spatial and temporal resolution of Magnetic Resonance Imaging makes it the election imaging modality to monitor in vivo the vascular volume changes. Commonly used MRI methods to obtain this information rely on the administration of contrast agents that modify the bulk water relaxation times but, unfortunately, they can provide only an estimate of vV since they are not fully retained in the vascular space. Herein, Gd-loaded Red Blood Cells (Gd-RBCs) are proposed as a contrast agent able to provide quantitative information on tumor vascularization. Being Gd-RBCs fully retained in the vascular space, the proposed method does not suffer for the limitations associated to the use of extracellular Gd-agents that quickly extravasate in the leaky tumor vasculature. Furthermore, the long half-life and biocompatibility of Gd-RBCs allows repeating the measurement many times upon their administration; this ensures the possibility to in vivo evaluate the change of vascular volume during tumor growth. For these reasons, Gd-RBCs may represent a highly biocompatible imaging reporter of vasculature, able to quantitatively assess changes in the vascular volume in the ROI.

Patient characteristics influencing the variability of distributed parameter-based models in DCE-CT kinetic analysis.

Kinetic parameter variability may be sensitive to kinetic model choice, kinetic model implementation or patient-specific effects. The purpose of this study was to assess their impact on the variability of dynamic contrast-enhanced computed tomography (DCE-CT) kinetic parameters. A total of 11 canine patients with sinonasal tumours received high signal-to-noise ratio, test-double retest DCE-CT scans. The variability for three distributed parameter (DP)-based models was assessed by analysis of variance. Mixed-effects modelling evaluated patient-specific effects. Inter-model variability (CVinter ) was comparable to or lower than intra-model variability (CVintra ) for blood flow (CVinter :[4-28%], CVintra :[28-31%]), fractional vascular volume (CVinter :[3-17%], CVintra :[16-19%]) and permeability-surface area product (CVinter :[5-12%], CVintra :[14-15%]). The kinetic models were significantly (P<0.05) impacted by patient characteristics for patient size, area underneath the curve of the artery and of the tumour. In conclusion, DP-based models demonstrated good agreement with similar differences between models and scans. However, high variability in the kinetic parameters and their sensitivity to patient size may limit certain quantitative applications.

3D BrainCV: Simultaneous visualization and analysis of cells and capillaries in a whole mouse brain with one-micron voxel resolution

Systematic cellular and vascular configurations are essential for understanding fundamental brain anatomy and metabolism. We demonstrated a 3D brainwide cellular and vascular (called 3D BrainCV) visualization and quantitative protocol for a whole mouse brain. We developed a modified Nissl staining method that quickly labeled the cells and blood vessels simultaneously in an entire mouse brain. Terabytes 3D datasets of the whole mouse brains, with unprecedented details of both individual cells and blood vessels, including capillaries, were simultaneously imaged at 1-μm voxel resolution using micro-optical sectioning tomography (MOST). For quantitative analysis, we proposed an automatic image-processing pipeline to perform brainwide vectorization and analysis of cells and blood vessels. Six representative brain regions from the cortex to the deep, including FrA, M1, PMBSF, V1, striatum, and amygdala, and six parameters, including cell number density, vascular length density, fractional vascular volume, distance from the cells to the nearest microvessel, microvascular length density, and fractional microvascular volume, had been quantitatively analyzed. The results showed that the proximity of cells to blood vessels was linearly correlated with vascular length density, rather than the cell number density. The 3D BrainCV made overall snapshots of the detailed picture of the whole brain architecture, which could be beneficial for the state comparison of the developing and diseased brain.

Hemodynamic Determinants of Perivascular Collateral Development in Swine Renal Artery Stenosis

Renal artery stenosis (RAS) resulting in reduced renal blood flow (RBF) is a common cause of secondary hypertension and deterioration of renal function, which may lead to end-stage renal disease. Recruitment and formation of periarterial collateral vessels may serve to bypass RAS and restore distal blood supply. We hypothesized that development of collaterals around RAS may preserve kidney function. Collateral formation index (CI) was assessed using multidetector computed tomography as fractional vascular volume surrounding the stenosis in 31 pigs with unilateral RAS. Single kidney RBF and glomerular filtration rate (GFR) were also measured. Of 25 pigs that developed significant stenosis (≥65%), 8 demonstrated minor collateral development (CI < 0.3), and 17 showed major collateral development (CI ≥ 0.3). The degree of RAS was significantly higher in pigs with major collaterals compared with pigs with minor collaterals, and poststenotic kidney cortical volume, perfusion, RBF, and GFR were significantly lower. In a subset of pigs matched for the degree of RAS, RBF and GFR remained lower in pigs with major collaterals. We conclude that collaterals develop in animals with significant RAS in proportion to its severity and might be triggered by distal injury, such as decreases in cortical volume and perfusion. However, development of collaterals was unable to confer measurable benefits for stenotic kidney function distal to severe RAS.

3D POWER DOPPLER IN OBSTETRICS

Flow is defined as the amount of fluid, ordinarily blood, passing per unit time (usually per minute). Perfusion is defined as the volume of blood flowing through a mass of tissue per unit time. The standard measure of perfusion is millilitres of fluid per second per 100 g of tissue (or 100 ml in volume) i.e. the fractional blood volume in an area divided by the mean transit time through the area, where the area is scaled to a 100 ml of tissue. The fractional vascular volume is an index of the physiological vascularity of a region and represents the proportion of tissue occupied by blood. Several ultrasound based techniques have been used in an attempt to quantify perfusion. Vessel dimensions of capillaries and arterioles are below the spatial resolution of even the latest ultrasound machines, and capillary flow is slower than that required to generate a Doppler signal which leads to underestimation of true perfusion. For all ultrasound-based techniques movement artefacts are probably the greatest obstacle to obtain quantitative information on perfusion. This review will discuss the technology and use of the ultrasound mode of three dimensional power Doppler, its benefits and limitations in estimating vascularity focusing on the field of obstetrics.

Reversal of Experimental Renovascular Hypertension Restores Coronary Microvascular Function and Architecture

Hypertension (HTN) may lead to left ventricular hypertrophy and vascular dysfunction, which are independent factors for adverse cardiovascular outcomes. We hypothesized that decreased blood pressure by percutaneous transluminal renal angioplasty (PTRA) would improve the function and architecture of coronary microvessels, in association with decreased inflammation and fibrosis. Three groups of pigs were studied: normal, HTN, and HTN+PTRA. After 6 weeks of renovascular HTN, induced by placing a local-irritant coil in the renal artery, pigs underwent PTRA or sham. Four weeks later multidetector-computed tomography (CT) was used to assess systolic, diastolic, and microvascular function, and responses to adenosine. Microvascular architecture, oxygen sensors, inflammation, and fibrosis were then explored in cardiac tissue. PTRA successfully decreased blood pressure and left ventricular hypertrophy. Basal fractional vascular volume (FVV) was similar among the groups, but its response to adenosine was significantly attenuated in HTN, whereas microvascular permeability (MP) and response to adenosine were greater than normal. Both were restored by PTRA. These were accompanied by increased myocardial expression of hypoxia-inducible factor (HIF)-1α, inflammation, and microvascular remodeling, including increased density of epicardial microvessels (20-200 µm), as well as cardiac diastolic dysfunction, all of which improved by reversal of HTN. However, PTRA only partially decreased myocardial fibrosis. Reversal of early renovascular HTN improved coronary microvascular function and architecture and reversed myocardial hypertrophy and diastolic dysfunction, in association with decreased levels of myocardial ischemia and inflammation markers, underscoring the benefits of blood pressure normalization for preservation of cardiovascular function and structure.

Dynamic contrast‐enhanced MRI of neuroendocrine hepatic metastases: A feasibility study using a dual‐input two‐compartment model

Neuroendocrine hepatic metastases exhibit various contrast uptake enhancement patterns in dynamic contrast-enhanced MRI. Using a dual-input two-compartment distributed parameter model, we analyzed the dynamic contrast-enhanced MRI datasets of seven patient study cases with the aim to relate the tumor contrast uptake patterns to parameters of tumor microvasculature. Simulation studies were also performed to provide further insights into the effects of individual microcirculatory parameter on the tumor concentration-time curves. Although the tumor contrast uptake patterns can be influenced by many parameters, initial results indicate that hepatic blood flow and the ratio of fractional vascular volume to fractional interstitial volume may potentially distinguish between the patterns of neuroendocrine hepatic metastases.

Monocyte Chemoattractant Proteins Mediate Myocardial Microvascular Dysfunction in Swine Renovascular Hypertension

Monocyte chemoattractant proteins (MCPs) play an important role in mediating inflammatory processes. Hypertension (HTN) is associated with inflammation as well as impaired cardiac microcirculatory function and structure, but the contribution of MCPs to these alterations remained unclear. This study tested the hypothesis that MCPs regulate cardiac microvascular function and structure in experimental HTN. Pigs (n=6 per group) were studied after 10 weeks of normal, renovascular HTN, or renovascular HTN+ bindarit (MCPs inhibitor, 50 mg/kg/d PO). Left ventricular (LV) function, myocardial microvascular permeability, and fractional vascular volume were assessed by fast computed tomography before and after adenosine infusion (400 microg/kg/min). Myocardial fibrosis, inflammation, and microvascular remodeling were determined ex vivo. Hypertension was not altered by bindarit, but LV hypertrophy and diastolic function were improved. In response to adenosine, myocardial microvascular permeability increased in HTN (from 0.0083+/-0.0009 to 0.0103+/-0.0011 AU, P=0.038 versus baseline) and fractional vascular volume decreased, whereas both remained unchanged in normal and HTN+bindarit pigs. HTN upregulated endothelin-1 expression, myocardial inflammation, and microvascular wall thickening, which were inhibited by bindarit. MCPs partly mediate myocardial inflammation, fibrosis, vascular remodeling, and impaired vascular integrity induced by hypertension. Inhibition of MCPs could potentially be a therapeutic target in hypertensive cardiomyopathy.

Comparative study of experiencedvsnon-experienced radiologists in assessing parametric CT images of the response of the prostate gland to radiotherapy

Functional CT can demonstrate acute quantitative increases in perfusion, permeability and fractional vascular volume in the prostate gland of patients with prostate cancer following radiotherapy (RT). We hypothesize that these quantitative changes can also be demonstrated visually by presenting them as colour parametric maps using custom software. 21 patients with prostate cancer were studied before, and 1-2 weeks after, RT. Repeated CT scans through a single section of the prostate was performed following contrast injection. Capillary permeability, fractional vascular volume and tissue perfusion were calculated and converted to colour maps using a customized Matlab imaging programme. Five "expert" and five "novice" radiologists scored pairs of randomized prostate images as an "increase", "decrease" or "no change" in intensity following RT. Kappa (kappa) statistics was used to assess the concordance of opinions. Significant quantitative increases in all indices occurred after RT, and almost all of the parametric images were scored as an increase in intensity following RT (perfusion = 95%, permeability = 88%, volume = 84%). There was substantial agreement between the experts and novices (kappa: perfusion = 0.93, permeability = 0.80, volume = 0.90), as well as within the expert (kappa: perfusion = 1, permeability = 0.86, volume = 1) and novice (kappa: perfusion = 0.82, permeability = 0.78, volume = 0.78) groups. Functional colour maps of the prostate can reliably portray the hyperaemic response following RT in a group with quantitative increases in perfusion, permeability and fractional vascular volume, and provides a potentially accessible and convenient method for image analysis by radiologists of varying experience.

Measurement of equine laminar blood flow and vascular permeability by use of dynamic contrast-enhanced computed tomography

To define the reference range for laminar blood flow (BF) and vascular permeability (VPM) in horses without laminitis by use of dynamic contrast-enhanced computed tomography (CT). 9 adult horses that were not lame and had no abnormalities of the laminae or phalanges detectable via radiographic examination. Each horse was anesthetized by use of a routine protocol. Horses were placed in right or left lateral recumbency with the dependent forelimb in the CT gantry; only 1 limb of each horse was scanned. Serial 10-mm collimated transverse CT images were acquired at the same location every other second for 90 seconds during infusion of ionic, iodinated contrast medium. Custom software was used to estimate BF, VPM, and fractional vascular volume (FVV) in the dorsal, dorsomedial, and dorsolateral laminar regions. Among the 9 horses' forelimbs, mean +/- SD dorsal laminar BF was 0.43 +/- 0.21 mL*min(1)*mL(1). Mean dorsomedial and dorsolateral laminar BFs were 0.26 +/- 0.16 mL*min(1)*mL(1) and 0.24 +/- 0.16 mL*min(1)*mL(1), respectively. Mean dorsal laminar VPM was 0.09 +/- 0.03 mL*min(1)*mL(1). Mean dorsomedial and dorsolateral laminar VPMs were 0.16 +/- 0.06 mL*min(1)*mL(1) and 0.12 +/- 0.06 mL*min(1)*mL(1), respectively. Mean dorsal laminar FVV was 0.63 +/- 0.20 and dorsomedial and dorsolateral laminar FVV were 0.37 +/- 0.14 and 0.34 +/- 0.17, respectively. In horses, laminar BF, VPM, and FVV can be non-invasively measured by use of dynamic contrast-enhanced CT.

Evaluation of Porcine Myocardial Microvascular Permeability and Fractional Vascular Volume Using 64-Slice Helical Computed Tomography (CT)

Myocardial microvascular permeability-surface area product (MPSP) and fractional vascular volume (FVV), indices of endothelial function and microvascular perfusion, can be noninvasively evaluated by electron beam computed tomography (EBCT), but it remains unknown whether comparable assessments can be obtained with 64-slice multidetector CT (CT-64). We studied 12 pigs with both EBCT and CT-64 in randomized order 1 week apart, before and during IV adenosine infusion. Myocardial attenuation changes in the cardiac wall were assessed after a central-venous injection of iopamidol. Time-attenuation curves were analyzed using both indicator-dilution and Patlak models to calculate MPSP and FVV. CT-64 and EBCT assessments of basal MPSP obtained by the Patlak method were similar (0.37 +/- 0.03 vs. 0.37 +/- 0.04 mL/min/g), as was its response to adenosine, and correlated significantly (r = 0.87). Patlak FVV was also similar between CT-64 and EBCT at baseline (0.08 +/- 0.02 vs. 0.07 +/- 0.02 mL blood/mL) and during adenosine, and correlated well (r = 0.93). MPSP and FVV estimated by the indicator-dilution method were not significantly correlated. CT-64 assessments of myocardial MPSP and FVV may not be reliable when using indicator-dilution analysis, likely due to its sensitivity to scan duration. However, CT-64 assessments obtained using the Patlak model are feasible.

Renal blood flow measurement with contrast-enhanced harmonic ultrasonography: evaluation of dopamine-induced changes in renal cortical perfusion in humans.

An accessible non-invasive method for evaluating renal regional blood flow in real time is highly desirable in the clinical setting. Recent progress in ultrasonography with microbubble contrast has allowed quantification of regional blood flow in animal models. Goal ofthis study was to establish a convenient contrast--enhanced harmonic ultrasonography (CEHU) method for evaluating renal cortical blood flow in humans. We carried out intermittent second harmonic imaging in 9 healthy volunteers. Pulse interval was progressively decreased from 4 s - 0.2 s during continuous venous infusion of the microbubble contrast agent. Pulse interval versus CEHU-derived acoustic intensity plots provided microbubble velocity (MV) and fractional vascular volume (FVV) during renal cortical perfusion in humans. Low-dose dopamine infusion (2 microg/min/kg) resulted in a significant increase in MV which correlated well with the increase in total renal blood flow (RBF) determined by a conventional study of p-aminohippurate clearance (C(PAH)) (r = 0.956, p < 0.0001). Although FVV was not significantly increased, alterations in CEHU-derived renal cortical blood flow calculated by the products of MV and FVV were also correlated with alterations in total RBF (r = 0.969, p < 0.0001). Thus, low-dose dopamine infusion increases renal cortical blood flow observed in CEHU, mainly by increasing MV. The present study shows that renal cortical blood flow in humans can be measured non-invasively by CEHU and that CEHU can be used for quantitatively evaluating changes induced by a therapeutic agent such as dopamine in flow velocity and in FVV.

Quantification of blood flow.

Traditionally, Doppler ultrasound has been used to estimate blood flow as the mean velocity multiplied by the vessel area, but this is subject to significant errors and may be difficult to perform accurately. Microbubbles, developed as contrast agents for ultrasound, were initially envisaged as useful for increasing the intensity of echoes and thus rescuing Doppler studies that were technical failures because of attenuated signals or very slow flow. However, they can act as tracers and, by analogy with isotope techniques, can be used to measure blood flow with transit-time methods which exploit both arterial and venous time-intensity data. An acceptable compromise is to acquire both a tissue intensity curve and one from the feeding artery. The transit of microbubbles across an organ or tissue can be used to estimate haemodynamic alterations, e.g. the arterialisation of the supply to the liver in malignancies and cirrhosis and the delayed arterio-venous transit in the transplant kidney during rejection. The fragility of microbubbles can be turned to advantage by being exploited to create a negative bolus by exposing a tissue slice to a high power beam. The rate of refilling of this slice by circulating microbubbles can then be followed with a low-intensity monitoring beam and the resulting rising exponential curve analysed to extract indices of both the reperfusion rate (the slope) and the fractional vascular volume (the asymptote). The product of these is a measure of true tissue perfusion.

Functional CT imaging of the acute hyperemic response to radiation therapy of the prostate gland: early experience.

Functional CT can measure perfusion and permeability. We hypothesized that acute changes could be measured in these indexes following radiation therapy (RT) to the prostate gland. Twenty-two patients with prostatic cancer were studied before and 1-2 and 6-12 weeks after RT. A single section through the prostate was repeatedly scanned after contrast medium bolus injection. Contrast agent clearance per unit volume (alpha/V) and fractional vascular volume (fvv) were calculated using Patlak graphical analysis. Perfusion was calculated as the ratio between maximal rate of tissue enhancement and peak arterial enhancement. Significant increases in all indexes occurred after RT. Mean perfusion rose from 0.122 to 0.263 ml/min/ml at 1-2 weeks, mean alpha/V increased from 0.0012 to 0.0016 ml/min/ml at 1-2 weeks, and mean fvv increased from 13.7 to 21% at 1-2 weeks. All three indexes remained elevated at 6-12 weeks after the start of RT. Functional CT demonstrated an acute hyperemic response following RT to the prostate gland.

F51Development of power Doppler as a quantifiable tool for assessing fetal perfusion: fractional renal vascular volume

BackgroundPower Doppler allows the display dynamic range to be increased by up to 10–25dB by coding the amplitude rather than the velocity component of the Doppler frequency shift. Though this means an improvement in image quality, the real advantage of the additional information coded within this signal lies in the potential for quantification of flow (as vascular volume).MethodIsolated measurements of amplitude do not have meaning unless they can be standardised to remove the effects of machine settings and attenuation. Two important functions are necessary for this: 1. Correction of the nonlinearities of the energy scale bar (purpose‐designed software ‐CQ Analysis, Kinetic Imaging Ltd, Liverpool). 2. Standardisation to a local area of 100% blood flow (the fetal aorta) to define a fractional regional vascular volume. Multiple clips of fetal renal perfusion were stored to mo disk using the Acuson SequoiaTM for offline computer analysis.Results150 fetuses were examined (24–40 weeks). Fetal vascular branching could be seen throughout the renal parenchyma in &gt; 80% of fetuses, with clear fluctuations in the fetal cardiac cycle and statistically significant energy values to the aorta and renal parenchyma. Standardising the peripheral volume flow to the aorta gives a fractional vascular volume of approximately 10–20%.ConclusionsFurther work is underway to improve reproducibility of this technique, to develop an accurate index of fetal renal perfusion.AcknowledgementsAlec Welsh is supported by a Research Training Fellowship from RCOG/WellBeing.

Imaging of tumour therapy responses by dynamic CT

The objective of this study was to investigate whether functional CT with Patlak analysis could be used to demonstrate acute changes associated with radiotherapy. Patlak analysis yields fractional vascular volume and contrast clearance per unit volume (a measure of permeability). Four tumour types (prostate, bronchus, breast and cervix) were studied pre-radiotherapy and at 1–2 weeks and 6–12 weeks post-therapy. Significant rises in fractional vascular volume and contrast clearance were shown at 1–2 weeks. These indices were still significantly elevated at 6–12 weeks post-therapy. In the prostates perfusion values were also elevated reflecting a hyperemic response to radiotherapy. Dynamic CT with Patlak analysis can be used to measure important pathophysiological indices which may prove useful in assessing response to therapy of tumours.

Use of contrast-enhanced computed tomography to measure clearance per unit renal volume: a novel measurement of renal function and fractional vascular volume.

The iodinated contrast agents used for computed tomography (CT) have pharmacokinetics similar to inulin and can measure physiological indices, such as clearance per unit renal volume (alpha/V) and fractional vascular volume (fvv). Clinical experience with these techniques is, however, scanty, and the present study explored their potential in subjects with and without renal dysfunction. In a series of subjects, a single slice of kidney was scanned sequentially after the bolus injection of contrast material. Time-attenuation curves were constructed, and alpha/V and fvv were calculated using a Patlak graphic analysis. In the first part of the study, 50 normal kidneys in 35 subjects (aged 21 to 75 years) were studied. In the second stage, alpha/V was compared with glomerular filtration rate (GFR) measurements in 24 patients with diabetes (aged 28 to 84 years) with or without renal dysfunction. In normal kidneys, alpha/V averaged 0.49 +/- 0.11 mL/min/mL and fvv averaged 35% +/- 12%. These values agree with literature data obtained using other techniques. A negative correlation was seen between age and alpha/V (r = 0.66; P < 0.0001), but not fvv. In patients with diabetes, a strong correlation was observed between renal clearance values, calculated from CT and corrected for renal volume, and GFR (r = 0.87; P < 0.0001). Dynamic CT can provide quantitative renal physiological information on a regional basis noninvasively.