Automatic Ischemic Core Estimation Based on Noncontrast-Enhanced Computed Tomography.

BACKGROUND: Evaluating the extent of ischemic change is an important step in deciding whether to use thrombolysis or mechanical thrombectomy, but the current standard method, Alberta Stroke Program Early CT Score, is semiquantitative and has low consistency among raters. We aim to create and test a fully automated machine learning-based ischemic core segmentation model using only noncontrast-enhanced computed tomography images. METHODS: In this multicenter retrospective study, patients with anterior circulation acute ischemic stroke who received both computed tomography (CT) and magnetic resonance imaging before thrombolysis or recanalization treatment between 2013 and 2019 were included. On CT, the ischemic core was manually delineated using the diffusion-weighted image and apparent diffusion coefficient maps. A deep learning-based ischemic core segmentation model (DL model) was developed using data from 3 institutions (n=272), and the model performance was validated using data from 3 institutions (n=106 Results: The median time ).between CT and magnetic resonance imaging in the validation cohort was 18 min. The DL model calculated ischemic core volume was significantly correlated with the reference standard (intraclass correlation coefficient, 0.90, P<0.01). Both the early time window (≤4.5 hours from onset; intraclass correlation coefficient, 0.90, P<0.01) and the late time window (>4.5 hours from onset; intraclass correlation coefficient, 0.93, P<0.01) had significant correlations. The median difference in ivolume between the model and the reference standard was 4.7 mL (interquartile range, 0.8-12.4 mL). The DL model performed well in distinguishing large ischemic cores (>70 mL), with a sensitivity of 84.2%, specificity of 97.7%, and area under the curve of 0.91. CONCLUSIONS: The deep learning-based ischemic core segmentation model, which was based on noncontrast-enhanced CT, demonstrated high accuracy in assessing ischemic core volume in patients with anterior circulation acute ischemic stroke.

Separating neuronal activity and systemic low-frequency oscillation related BOLD responses at nodes of the default mode network during resting-state fMRI with multiband excitation echo-planar imaging.

Functional magnetic resonance imaging (fMRI) evaluates brain activity using blood oxygenation level-dependent (BOLD) contrast. Resting-state fMRI (rsfMRI) examines spontaneous brain function using BOLD in the absence of a task, and the default mode network (DMN) has been identified from that. The DMN is a set of nodes within the brain that appear to be active and in communication when the subject is in an awake resting state. In addition to signal changes related to neural activity, it is thought that the BOLD signal may be affected by systemic low-frequency oscillations (SysLFOs) that are non-neuronal in source and likely propagate throughout the brain to arrive at different regions at different times. However, it may be difficult to distinguish between the response due to neuronal activity and the arrival of a SysLFO in specific regions. Conventional single-shot EPI (Conv) acquisition requires a longish repetition time, but faster image acquisition has recently become possible with multiband excitation EPI (MB). In this study, we evaluated the time-lag between nodes of the DMN using both Conv and MB protocols to determine whether it is possible to distinguish between neuronal activity and SysLFO related responses during rsfMRI. While the Conv protocol data suggested that SysLFOs substantially influence the apparent time-lag of neuronal activity, the MB protocol data implied that the effects of SysLFOs and neuronal activity on the BOLD response may be separated. Using a higher time-resolution acquisition for rsfMRI might help to distinguish neuronal activity induced changes to the BOLD response from those induced by non-neuronal sources.

Artificial Intelligence Trained by Deep Learning Can Improve Computed Tomography Diagnosis of Nontraumatic Subarachnoid Hemorrhage by Nonspecialists.

Subarachnoid hemorrhage (SAH) is a serious cerebrovascular disease with a high mortality rate and is known as a disease that is hard to diagnose because it may be overlooked by noncontrast computed tomography (NCCT) examinations that are most frequently used for diagnosis. To create a system preventing this oversight of SAH, we trained artificial intelligence (AI) with NCCT images obtained from 419 patients with nontraumatic SAH and 338 healthy subjects and created an AI system capable of diagnosing the presence and location of SAH. Then, we conducted experiments in which five neurosurgery specialists, five nonspecialists, and the AI system interpreted NCCT images obtained from 135 patients with SAH and 196 normal subjects. The AI system was capable of performing a diagnosis of SAH with equal accuracy to that of five neurosurgery specialists, and the accuracy was higher than that of nonspecialists. Furthermore, the diagnostic accuracy of four out of five nonspecialists improved by interpreting NCCT images using the diagnostic results of the AI system as a reference, and the number of oversight cases was significantly reduced by the support of the AI system. This is the first report demonstrating that an AI system improved the diagnostic accuracy of SAH by nonspecialists.

Alberta Stroke Program Early CT Score Calculation Using the Deep Learning-Based Brain Hemisphere Comparison Algorithm.

OBJECTIVES: The Alberta Stroke Program Early Computed Tomography Score (ASPECTS) is a promising tool for the evaluation of stroke expansion to determine suitability for reperfusion therapy. The aim of this study was to validate deep learning-based ASPECTS calculation software that utilizes a three-dimensional fully convolutional network-based brain hemisphere comparison algorithm (3D-BHCA). MATERIALS AND METHODS: We retrospectively collected head non-contrast computed tomography (CT) data from 71 patients with acute ischemic stroke and 80 non-stroke patients. The results for ASPECTS on CT assessed by 5 stroke neurologists and by the 3D-BHCA model were compared with the ground truth by means of region-based and score-based analyses. RESULTS: In total, 151 patients and 3020 (151 × 20) ASPECTS regions were investigated. Median time from onset to CT was 195 min in the stroke patients. In region-based analysis, the sensitivity (0.80), specificity (0.97), and accuracy (0.96) of the 3D-BHCA model were superior to those of stroke neurologists. The sensitivity (0.98), specificity (0.92), and accuracy (0.97) of dichotomized ASPECTS > 5 analysis and the intraclass correlation coefficient (0.90) in total score-based analysis of the 3D-BHCA model were superior to those of stroke neurologists overall. When patients with stroke were stratified by onset-to-CT time, the 3D-BHCA model exhibited the highest performance to calculate ASPECTS, even in the earliest time period. CONCLUSIONS: The automated ASPECTS calculation software we developed using a deep learning-based algorithm was superior or equal to stroke neurologists in performing ASPECTS calculation in patients with acute stroke and non-stroke patients.

Ferumoxytol-enhanced cardiovascular magnetic resonance detection of early stage acute myocarditis.

BACKGROUND: The diagnostic utility of cardiovascular magnetic resonance (CMR) is limited during the early stages of myocarditis. This study examined whether ferumoxytol-enhanced CMR (FE-CMR) could detect an earlier stage of acute myocarditis compared to gadolinium-enhanced CMR. METHODS: Lewis rats were induced to develop autoimmune myocarditis. CMR (3 T, GE Signa) was performed at the early- (day 14, n = 7) and the peak-phase (day 21, n = 8) of myocardial inflammation. FE-CMR was evaluated as % myocardial dephasing signal loss on gradient echo images at 6 and 24 h (6 h- & 24 h-FE-CMR) following the administration of ferumoxytol (300µmolFe/kg). Pre- and post-contrast T2* mapping was also performed. Early (EGE) and late (LGE) gadolinium enhancement was obtained after the administration of gadolinium-DTPA (0.5 mmol/kg) on day 14 and 21. Healthy rats were used as control (n = 6). RESULTS: Left ventricular ejection fraction (LVEF) was preserved at day 14 with inflammatory cells but no fibrosis seen on histology. EGE and LGE at day 14 both showed limited myocardial enhancement (EGE: 11.7 ± 15.5%; LGE: 8.7 ± 8.7%; both p = ns vs. controls). In contrast, 6 h-FE-CMR detected extensive myocardial signal loss (33.2 ± 15.0%, p = 0.02 vs. EGE and p < 0.01 vs. LGE). At day 21, LVEF became significantly decreased (47.4 ± 16.4% vs control: 66.2 ± 6.1%, p < 0.01) with now extensive myocardial involvement detected on EGE, LGE, and 6 h-FE-CMR (41.6 ± 18.2% of LV). T2* mapping also detected myocardial uptake of ferumoxytol both at day 14 (6 h R2* = 299 ± 112 s- 1vs control: 125 ± 26 s- 1, p < 0.01) and day 21 (564 ± 562 s- 1, p < 0.01 vs control). Notably, the myocardium at peak-phase myocarditis also showed significantly higher pre-contrast T2* (27 ± 5 ms vs control: 16 ± 1 ms, p < 0.001), and the extent of myocardial necrosis had a strong positive correlation with T2* (r = 0.86, p < 0.001). CONCLUSIONS: FE-CMR acquired at 6 h enhance detection of early stages of myocarditis before development of necrosis or fibrosis, which could potentially enable appropriate therapeutic intervention.

Development of anisotropic phantoms using wood and fiber materials for diffusion tensor imaging and diffusion kurtosis imaging.

OBJECTIVE: Several studies have demonstrated that anisotropic phantoms can be utilized for diffusion magnetic resonance imaging. The purpose of our study was to examine whether wood is suitable as an anisotropic phantom material from the viewpoints of affordability and availability. In the current study, wood was used for restricted diffusion, and fibers were used for hindered diffusion. MATERIALS AND METHODS: Wood and fiber phantoms were made. Diffusion kurtosis images were acquired with three magnetic resonance scanners. Fractional anisotropy, radial diffusivity, axial diffusivity, radial kurtosis and axial kurtosis values were measured. The wood phantom was imaged, and its durability was confirmed. The phantoms were imaged in varying orientations within the magnetic field. The wood was observed using an optical microscope. RESULTS: Ten kinds of wood and the fiber had a diffusion metrics. The wood diffusion metrics suggested low variation over a period of 9 months. Changing the orientation of the phantoms within the magnetic field resulted in changes in diffusion metrics. Observation of wood vessels and fibers was conducted. DISCUSSION: Wood and fibers have anisotropy and are promising as phantom materials. The development of anisotropic phantoms that anyone can use is useful for diffusion magnetic resonance imaging research and clinical applications.

Myocardial viability of the peri-infarct region measured by T1 mapping post manganese-enhanced MRI correlates with LV dysfunction.

BACKGROUND: Manganese-enhanced MRI (MEMRI) detects viable cardiomyocytes based on the intracellular manganese uptake via L-type calcium-channels. This study aimed to quantify myocardial viability based on manganese uptake by viable myocardium in the infarct core (IC), peri-infarct region (PIR) and remote myocardium (RM) using T1 mapping before and after MEMRI and assess their association with cardiac function and arrhythmogenesis. METHODS: Fifteen female swine had a 60-minute balloon ischemia-reperfusion injury in the LAD. MRI (Signa 3T, GE Healthcare) and electrophysiological study (EPS) were performed 4 weeks later. MEMRI and delayed gadolinium-enhanced MRI (DEMRI) were acquired on LV short axis. The DEMRI positive total infarct area was subdivided into the regions of MEMRI-negative non-viable IC and MEMRI-positive viable PIR. T1 mapping was performed to evaluate native T1, post-MEMRI T1, and delta R1 (R1post-R1pre, where R1 equals 1/T1) of each territory. Their correlation with LV function and EPS data was assessed. RESULTS: PIR was characterized by intermediate native T1 (1530.5 ±â€¯75.2 ms) compared to IC (1634.7 ±â€¯88.4 ms, p = 0.001) and RM (1406.4 ±â€¯37.9 ms, p < 0.0001). Lower post-MEMRI T1 of PIR (1136.3 ±â€¯99.6 ms) than IC (1262.6 ±â€¯126.8 ms, p = 0.005) and higher delta R1 (0.23 ±â€¯0.08 s-1) of PIR than IC (0.18 ±â€¯0.09 s-1, p = 0.04) indicated higher myocardial manganese uptake of PIR compared to IC. Post-MEMRI T1 (r = -0.57, p = 0.02) and delta R1 (r = 0.51, p = 0.04) of PIR correlated significantly with LVEF. CONCLUSIONS: PIR is characterized by higher manganese uptake compared to the infarct core. In the subacute phase post-IR, PIR viability measured by post-MEMRI T1 correlates with cardiac function.

DEVELOPMENT OF RADIATION DOSE CALCULATION SOFTWARE USING THE SIZE-SPECIFIC DOSE ESTIMATE.

We aimed to develop a software for facilitating absorbed dose per pixel (pixel dose) calculation using a size-specific dose estimate (SSDE). We calculated the pixel dose at nine equal points inserted into the radiophotoluminescence glass dosemeter (RPLD) and compared the pixel dose with the measured doses using RPLD. With this method, the relative errors of average pixel dose was -0.1% for adults and 2.86, 3.36 and 1.17% for those aged 10, 5 and 1 years without tube current modulation, respectively. In contrast, the relative error of SSDE was 17.37% for adults and 20.38, 20.73 and 19.20% for those aged 10, 5 and 1 years, respectively. In other words, the pixel dose was almost equal to the measured doses. Therefore, our software can be useful for determining arbitrary point.

Dose-Dependent Cardioprotection of Moderate (32°C) Versus Mild (35°C) Therapeutic Hypothermia in Porcine Acute Myocardial Infarction.

OBJECTIVES: The study investigated whether a dose response exists between myocardial salvage and the depth of therapeutic hypothermia. BACKGROUND: Cardiac protection from mild hypothermia during acute myocardial infarction (AMI) has yielded equivocal clinical trial results. Rapid, deeper hypothermia may improve myocardial salvage. METHODS: Swine (n = 24) undergoing AMI were assigned to 3 reperfusion groups: normothermia (38°C) and mild (35°C) and moderate (32°C) hypothermia. One-hour anterior myocardial ischemia was followed by rapid endovascular cooling to target reperfusion temperature. Cooling began 30 min before reperfusion. Target temperature was reached before reperfusion and was maintained for 60 min. Infarct size (IS) was assessed on day 6 using cardiac magnetic resonance, triphenyl tetrazolium chloride, and histopathology. RESULTS: Triphenyl tetrazolium chloride area at risk (AAR) was equivalent in all groups (p = 0.2), but 32°C exhibited 77% and 91% reductions in IS size per AAR compared with 35°C and 38°C, respectively (AAR: 38°C, 45 ± 12%; 35°C, 17 ± 10%; 32°C, 4 ± 4%; p < 0.001) and comparable reductions per LV mass (LV mass: 38°C, 14 ± 5%; 35°C, 5 ± 3%; 32°C 1 ± 1%; p < 0.001). Importantly, 32°C showed a lower IS AAR (p = 0.013) and increased immunohistochemical granulation tissue versus 35°C, indicating higher tissue salvage. Delayed-enhancement cardiac magnetic resonance IS LV also showed marked reduction at 32°C (38°C: 10 ± 4%, p < 0.001; 35°C: 8 ± 3%; 32°C: 3 ± 2%, p < 0.001). Cardiac output on day 6 was only preserved at 32°C (reduction in cardiac output: 38°C, -29 ± 19%, p = 0.041; 35°C: -17 ± 33%; 32°C: -1 ± 28%, p = 0.041). Using linear regression, the predicted IS reduction was 6.7% (AAR) and 2.1% (LV) per every 1°C reperfusion temperature decrease. CONCLUSIONS: Moderate (32°C) therapeutic hypothermia demonstrated superior and near-complete cardioprotection compared with 35°C and control, warranting further investigation into clinical applications.

Comparison of Glass Capillary Plates and Polyethylene Fiber Bundles as Phantoms to Assess the Quality of Diffusion Tensor Imaging.

PURPOSE: The purpose of this study was to evaluate the suitability of two phantoms, one made of capillary plates and the other polyethylene fibers, for assessing the quality of diffusion tensor imaging (DTI). METHODS: The first phantom was a stack of glass capillary plates with many parallel micropores (CP). The second phantom was a bundle of polyethylene fiber Dyneema held together with a thermal shrinkage tube (Dy). High resolution multi-shot echo planar imaging (EPI) DTI acquisitions were performed at b-values of 0 and 1000 s/mm2 and diffusion-times (Tdiff) of 37.7 and 97.7 ms on a preclinical 7T MRI scanner. Thirty diffusion-encoding directions were used. The data were used to calculate the fractional anisotropy (FA), mean diffusivity (MD), and angular dispersion (AD). Further acquisitions were performed at b-values from 0 to 8000 s/mm2 in 14 steps with the diffusion gradient applied parallel (axial) and perpendicular (radial) to the Z direction. On the other hand, the data acquired with a 3T MRI scanner were used to confirm that measurements on a clinical machine are consistent with the 7T MRI results. RESULTS: The dependence of FA, MD and AD on Tdiff was smaller for the Dy than for the CPs. The b-value-dependent signal attenuations in the axial direction at Tdiff = 37.7 and 97.7 ms were similar for both phantoms. In the radial direction, Dy demonstrated similar b-value attenuation to that of in vivo tissue for both Tdiffs, but the attenuation for the CPs was affected by the change in Tdiff. Parameter estimates were similar for 3T and 7T MRI. CONCLUSION: The characteristics of the CP indicate that it can be used as a restricted-diffusion dominant phantom, while the characteristics of the Dy suggest that it can be used as a hindered-diffusion dominant phantom. Dy may be more suitable than CP for DTI quality control.

Paracrine Effects of the Pluripotent Stem Cell-Derived Cardiac Myocytes Salvage the Injured Myocardium.

RATIONALE: Cardiac myocytes derived from pluripotent stem cells have demonstrated the potential to mitigate damage of the infarcted myocardium and improve left ventricular ejection fraction. However, the mechanism underlying the functional benefit is unclear. OBJECTIVE: To evaluate whether the transplantation of cardiac-lineage differentiated derivatives enhance myocardial viability and restore left ventricular ejection fraction more effectively than undifferentiated pluripotent stem cells after a myocardial injury. Herein, we utilize novel multimodality evaluation of human embryonic stem cells (hESCs), hESC-derived cardiac myocytes (hCMs), human induced pluripotent stem cells (iPSCs), and iPSC-derived cardiac myocytes (iCMs) in a murine myocardial injury model. METHODS AND RESULTS: Permanent ligation of the left anterior descending coronary artery was induced in immunosuppressed mice. Intramyocardial injection was performed with (1) hESCs (n=9), (2) iPSCs (n=8), (3) hCMs (n=9), (4) iCMs (n=14), and (5) PBS control (n=10). Left ventricular ejection fraction and myocardial viability, measured by cardiac magnetic resonance imaging and manganese-enhanced magnetic resonance imaging, respectively, was significantly improved in hCM- and iCM-treated mice compared with pluripotent stem cell- or control-treated mice. Bioluminescence imaging revealed limited cell engraftment in all treated groups, suggesting that the cell secretions may underlie the repair mechanism. To determine the paracrine effects of the transplanted cells, cytokines from supernatants from all groups were assessed in vitro. Gene expression and immunohistochemistry analyses of the murine myocardium demonstrated significant upregulation of the promigratory, proangiogenic, and antiapoptotic targets in groups treated with cardiac lineage cells compared with pluripotent stem cell and control groups. CONCLUSIONS: This study demonstrates that the cardiac phenotype of hCMs and iCMs salvages the injured myocardium effectively than undifferentiated stem cells through their differential paracrine effects.

Novel MRI Contrast Agent from Magnetotactic Bacteria Enables In Vivo Tracking of iPSC-derived Cardiomyocytes.

Therapeutic delivery of human induced pluripotent stem cell (iPSC)-derived cardiomyocytes (iCMs) represents a novel clinical approach to regenerate the injured myocardium. However, methods for robust and accurate in vivo monitoring of the iCMs are still lacking. Although superparamagnetic iron oxide nanoparticles (SPIOs) are recognized as a promising tool for in vivo tracking of stem cells using magnetic resonance imaging (MRI), their signal persists in the heart even weeks after the disappearance of the injected cells. This limitation highlights the inability of SPIOs to distinguish stem cell viability. In order to overcome this shortcoming, we demonstrate the use of a living contrast agent, magneto-endosymbionts (MEs) derived from magnetotactic bacteria for the labeling of iCMs. The ME-labeled iCMs were injected into the infarcted area of murine heart and probed by MRI and bioluminescence imaging (BLI). Our findings demonstrate that the MEs are robust and effective biological contrast agents to track iCMs in an in vivo murine model. We show that the MEs clear within one week of cell death whereas the SPIOs remain over 2 weeks after cell death. These findings will accelerate the clinical translation of in vivo MRI monitoring of transplanted stem cell at high spatial resolution and sensitivity.

Development of 1.45-mm resolution four-layer DOI-PET detector for simultaneous measurement in 3T MRI.

Recently, various types of PET-MRI systems have been developed by a number of research groups. However, almost all of the PET detectors used in these PET-MRI systems have no depth-of-interaction (DOI) capability. The DOI detector can reduce the parallax error and lead to improvement of the performance. We are developing a new PET-MRI system which consists of four-layer DOI detectors positioned close to the measured object to achieve high spatial resolution and high scanner sensitivity. As a first step, we are investigating influences the PET detector and the MRI system have on each other using a prototype four-layer DOI-PET detector. This prototype detector consists of a lutetium yttrium orthosilicate crystal block and a 4 × 4 multi-pixel photon counter array. The size of each crystal element is 1.45 mm × 1.45 mm × 4.5 mm, and the crystals are arranged in 6 × 6 elements × 4 layers with reflectors. The detector and some electric components are packaged in an aluminum shielding box. Experiments were carried out with 3.0 T MRI (GE, Signa HDx) and a birdcage-type RF coil. We demonstrated that the DOI-PET detector was normally operated in simultaneous measurements with no influence of the MRI measurement. A slight influence of the PET detector on the static magnetic field of the MRI was observed near the PET detector. The signal-to-noise ratio was decreased by presence of the PET detector due to environmental noise entering the MRI room through the cables, even though the PET detector was not powered up. On the other hand, no influence of electric noise from the PET detector in the simultaneous measurement on the MRI images was observed, even though the PET detector was positioned near the RF coil.

[MRI image reconstruction using polar-coordinates conversion of k-space data].

In this study, we proposed the new reconstruction techniques for magnetic resonance imaging (MRI) using filtered back projection (FBP) or simultaneous reconstruction technique (SIRT). We converted the k-space which was acquired by conventional phase-encoding schemes from Cartesian coordinates to polar coordinates and created the projection. The linear interpolation and the sinc interpolation were used in the conversion. The accuracy of the reconstructed image using projection was evaluated by the relative error in comparison with the standard image which was reconstructed by the two-dimensional Fourier transform (2DFT) with conventional Cartesian k-space. The relative error reconstructed both FBP and SIRT from projection with sinc interpolation is 0.013. The maximum value of standard image is 1.501451, FBP is 1.47921, and SIRT with iteration 100 is 1.44858 and with iteration 200 is 1.579442. The minimum value of both the standard image and the others is about 0. Visually, there is no margin between the standard image and the reconstructed image from projection with FBP or SIRT.

Experimental verification of age-dependent cisplatin-induced nephrotoxicity in rats using dynamic contrast-enhanced computed tomography.

PURPOSE: The aim of this study was to investigate age-dependent cisplatin-induced nephrotoxicity in rats using dynamic contrast-enhanced computed tomography (DCE-CT). MATERIALS AND METHODS: The DCE-CT studies were performed in 23 rats aged 4 weeks (n = 6), 6 weeks (n = 6), 8 weeks (n = 6), and 24 weeks (n = 5) on days 0, 2, 4, and 7. The rats were given intraperitoneally cisplatin 3.6 mg/kg body weight (BW) on day 0. The contrast clearance per unit renal volume (K (1)) was estimated using the Patlak model, and that of the entire kidney (K) was obtained by multiplying K(1) by the renal volume (V). RESULTS: On day 0, the K(1) value increased up to 8 weeks and dropped thereafter. The V and K values increased with age. The K value per unit BW was maximum at 4 weeks, remained relatively unchanged between 6 and 8 weeks, and dropped thereafter. The BW, K(1), and K values normalized by those on day 0 became lower in old rats than in young ones, and the differences among rats of different ages became greater with days after cisplatin injection, indicating that the cisplatin-induced nephrotoxicity becomes more severe with age. CONCLUSION: This study demonstrated the existence of age-dependent difference in cisplatin-induced nephrotoxicity in rats.

Quantitative assessment of early experimental diabetes in rats using dynamic contrast-enhanced computed tomography.

PURPOSE: To quantitatively assess the time course of changes of the renal volume and function in the early phase of streptozotocin (STZ)-induced diabetes in rats using dynamic contrast-enhanced computed tomography (DCE-CT). METHODS: The DCE-CT studies were performed in 24 male Sprague-Dawley rats (n=6 for control and n=18 for STZ-treated group) on days 0, 4, 7, 11, and 14 using a multi-detector row CT. The rats of an STZ-treated group were given intraperitoneally 65mg/kg body weight of STZ on day 0, and were divided into two groups based on the blood glucose concentration on day 4 being less than 300mg/dL [STZ-treated group (L), n=8] or greater than 300mg/dL [STZ-treated group (G), n=10]. The contrast clearance per unit renal volume (K(1)) was estimated from the DCE-CT data using the Patlak model. The renal volume (V(CT)) was calculated by manually delineating the kidney on the contrast-enhanced CT image. The contrast clearance of the entire kidney (K) was obtained by K(1)xV(CT). RESULTS: V(CT) in the STZ-treated group was significantly enlarged on day 4 compared to that on day 0 and continued until day 14. Although there were no significant changes in the time course of K(1) in all groups, K in the STZ-treated groups (L) and (G) significantly increased on days 7 and 4, respectively, and continued until day 14, suggesting that hyperfiltration occurs in parallel with renal volume enlargement. CONCLUSION: The present method appears useful for quantitatively evaluating the time course of STZ-induced diabetes in rats, because it allows repeated and simultaneous evaluation of renal morphology and function.