Theoretical investigation of transgastric and intraductal approaches for ultrasound-based thermal therapy of the pancreas.

BACKGROUND: The goal of this study was to theoretically investigate the feasibility of intraductal and transgastric approaches to ultrasound-based thermal therapy of pancreatic tumors, and to evaluate possible treatment strategies. METHODS: This study considered ultrasound applicators with 1.2 mm outer diameter tubular transducers, which are inserted into the tissue to be treated by an endoscopic approach, either via insertion through the gastric wall (transgastric) or within the pancreatic duct lumen (intraductal). 8 patient-specific, 3D, transient, biothermal and acoustic finite element models were generated to model hyperthermia (n = 2) and ablation (n = 6), using sectored (210°-270°, n = 4) and 360° (n = 4) transducers for treatment of 3.3-17.0 cm3 tumors in the head (n = 5), body (n = 2), and tail (n = 1) of the pancreas. A parametric study was performed to determine appropriate treatment parameters as a function of tissue attenuation, blood perfusion rates, and distance to sensitive anatomy. RESULTS: Parametric studies indicated that pancreatic tumors up to 2.5 or 2.7 cm diameter can be ablated within 10 min with the transgastric and intraductal approaches, respectively. Patient-specific simulations demonstrated that 67.1-83.3% of the volumes of four sample 3.3-11.4 cm3 tumors could be ablated within 3-10 min using transgastric or intraductal approaches. 55.3-60.0% of the volume of a large 17.0 cm3 tumor could be ablated using multiple applicator positions within 20-30 min with either transgastric or intraductal approaches. 89.9-94.7% of the volume of two 4.4-11.4 cm3 tumors could be treated with intraductal hyperthermia. Sectored applicators are effective in directing acoustic output away from and preserving sensitive structures. When acoustic energy is directed towards sensitive structures, applicators should be placed at least 13.9-14.8 mm from major vessels like the aorta, 9.4-12.0 mm from other vessels, depending on the vessel size and flow rate, and 14 mm from the duodenum. CONCLUSIONS: This study demonstrated the feasibility of generating shaped or conformal ablative or hyperthermic temperature distributions within pancreatic tumors using transgastric or intraductal ultrasound.

Effects of aging on glomerular function and number in living kidney donors.

To elucidate the pathophysiologic changes in the kidney due to aging, we used physiological, morphometric, and imaging techniques to quantify GFR and its determinants in a group of 24 older (≥ 55 years) compared to 33 younger (≤ 45 years) living donors. Mathematical modeling was used to estimate the glomerular filtration coefficients for the whole kidney (K(f)) and for single nephrons (SNK(f)), as well as the number of filtering glomeruli (N(FG)). Compared to younger donors, older donors had a modest (15%) but significant depression of pre-donation GFR. Mean whole-kidney K(f), renocortical volume, and derived N(FG) were also significantly decreased in older donors. In contrast, glomerular structure and SNK(f) were not different in older and younger donors. Derived N(FG) in the bottom quartile of older donors was less than 27% of median-derived N(FG) in the two kidneys of younger donors. Nevertheless, the remaining kidney of older donors exhibited adaptive hyperfiltration and renocortical hypertrophy post-donation, comparable to that of younger donors. Thus, our study found the decline of GFR in older donors is due to a reduction in K(f) attributable to glomerulopenia. We recommend careful monitoring for and control of post-donation comorbidities that could exacerbate glomerular loss.

Can single-kidney glomerular filtration rate be determined with contrast-enhanced CT?

Daghini et al used a pig model to estimate single-kidney GFR with dynamic contrast-enhanced CT scanning. Three techniques were evaluated, two of which (the modified Patlak method and the gamma variate model) yielded GFR estimates that correlated significantly with determinations made by using standard inulin clearance techniques. The findings hold promise that noninvasive in vivo assessment of single-kidney renal function may be achieved in patients.

Estimation of renal extraction fraction based on postcontrast venous and arterial differential T1 values: an error analysis.

An error analysis for quantifying single kidney extraction fraction (EF) via differential T1 measurements in the renal vein (RV) and renal artery (RA) is presented. Sources of error include blood flow effects, the effect of a short repetition time (TR), and the impact of uncertainties in the T1 estimates on the final EF calculations. Blood flow effects were investigated via simulation. For a range of blood velocities in the renal vein that may be found in kidney disease, incomplete refreshment of blood between readouts results in significant errors in T1 estimation. For a .5-cm slice, 110-ms sampling interval, and T1 of 600 ms, T1 estimation to within 5% of true T1 requires an average through-plane velocity of 6.75 cm/s for parabolic flow, and 3.5 cm/s for plug flow. Improvement can be achieved by accurately estimating the fraction of blood that has not refreshed between readouts (f(old)), while the quality of the T1 estimate varies with the accuracy of f(old) estimation. Shortening of the TR was investigated using phantom and in vivo studies. T1 was estimated to within 3% of the true value on phantoms, and within 5% of the true value for flowing blood for TR = 2T1. The estimated EF is shown to be very sensitive to the difference between T(1RA) and T(1RV). To achieve 10% or 20% uncertainty in the EF estimate, T1 in the renal vein and renal artery must be estimated to within approximately 1% or 2%. Because of limitations on measurement accuracy and precision, this method appears to be impractical at this time.

Effects of spatial and temporal resolution for MR image-guided thermal ablation of prostate with transurethral ultrasound.

PURPOSE: To describe approaches for determining optimal spatial and temporal resolutions for the proton resonance frequency shift method of quantitative magnetic resonance temperature imaging (MRTI) guidance of transurethral ultrasonic prostate ablation. MATERIALS AND METHODS: Temperature distributions of two transurethral ultrasound applicators (90 degrees sectored tubular and planar arrays) for canine prostate ablation were measured via MRTI during in vivo sonication, and agree well with two-dimensional finite difference model simulations at various spatial resolutions. Measured temperature distributions establish the relevant signal-to-noise ratio (SNR) range for thermometry in an interventional MR scanner, and are reconstructed at different resolutions to compare resultant temperature measurements. Various temporal resolutions are calculated by averaging MRTI frames. RESULTS: When noise is added to simulated temperature distributions for tubular and planar applicators, the minimum root mean squared (RMS) error is achieved by reconstructing to pixel sizes of 1.9 and 1.7 mm, respectively. In in vivo measurements, low spatial resolution MRTI data are shown to reduce the noise without significantly affecting thermal dose calculations. Temporal resolution of 0.66 frames/minute leads to measurement errors of more than 12 degrees C during rapid heating. CONCLUSION: Optimizing MRTI pixel size entails balancing large pixel SNR gain with accuracy in representing underlying temperature distributions.

Single breath-hold diffusion-weighted imaging of the abdomen.

PURPOSE: To generate high quality diffusion-weighted images (DWI) and corresponding isotropic ADC maps of the abdomen with full organ (kidneys) coverage in a single breath-hold. MATERIALS AND METHODS: DWI was performed in 12 healthy subjects with an asymmetric, spin-echo, single-shot EPI readout on a system with high performance gradients (40 mT/minute). The isotropic diffusion coefficient was measured from maps and SNR was determined for both diffusion-weighted and reference images in the liver, spleen, pancreas, and kidneys. In six patients, single-axis diffusion encoding along three orthogonal axes (12 NEX) was employed to assess anisotropic diffusion in kidneys. RESULTS: This technique yielded images of quality and resolution which compares favorably to that of prior work. SNR ranged from 27.0 in liver to 44.1 in kidneys for the diffusion-weighted images, and from 19.6 in liver to 39.0 in kidneys in reference images. ADCs obtained in the renal medulla, renal cortex, liver, spleen, and pancreas were (2091 +/- 55) x 10(-6), (2580 +/- 53) x 10(-6), (1697 +/- 52) x 10(-6), (1047 +/- 82) x 10(-6), and (2605 +/- 168) x 10(-6) mm(2)/second, respectively (mean +/- SE). Apparent diffusion coefficient (ADC) in the renal medulla and cortex were significantly different by paired t-test (P = 4.22 x 10(-10)). Renal medulla and cortex yielded anisotropy indices (AI) of 0.129 and 0.067, respectively. CONCLUSIONS: 1) Single-shot SE EPI DWI in the abdomen with this technique provides high quality images and maps with full organ coverage in a single breath-hold; 2) ADCs obtained in the renal medulla and cortex are significantly different; and 3) diffusion within the renal medulla is moderately anisotropic.

Noninvasive measurement of extraction fraction and single-kidney glomerular filtration rate with MR imaging in swine with surgically created renal arterial stenoses.

PURPOSE: To test whether magnetic resonance (MR) imaging enables accurate measurement of extraction fraction (EF) in swine with unilateral renal ischemia and to evaluate effects of renal arterial stenosis on EF and single-kidney glomerular filtration rate. MATERIALS AND METHODS: High-grade unilateral renal arterial stenoses were surgically created in eight pigs. Direct measurements of renal venous and arterial inulin concentration provided reference standard estimates of single-kidney EF. Pigs were imaged with a 1.5-T imager to estimate EF, renal blood flow, and glomerular filtration rate. A breath-hold inversion-recovery spiral sequence was used to measure T1 of blood in the infrarenal inferior vena cava and renal veins after intravenous administration of gadopentetate dimeglumine, and these data were used to calculate EF. Cine-phase contrast material-enhanced imaging of the renal arteries provided quantitative renal blood flow measurements. Bilateral single-kidney glomerular filtration rate was then determined: glomerular filtration rate = renal blood flow x (1 - hematocrit level) x EF. RESULTS: A statistically significant linear correlation was found between EF, as determined with MR imaging, and inulin (r = 0.77). As compared with kidneys without renal arterial stenosis, kidneys with renal arterial stenosis showed 50% (0.14/0.28) EF reduction (P <.01) and 59% glomerular filtration rate reduction (P <.01). CONCLUSION: MR imaging shows promise for in vivo measurement of EF and glomerular filtration rate, which may be useful in assessing the clinical importance of renal arterial stenosis.

Measurement of renal volumes with contrast-enhanced MRI.

PURPOSE: To determine the accuracy of in vivo magnetic resonance imaging (MRI) measurement of total renal parenchymal volume and medullary fraction. MATERIALS AND METHODS: Sixteen kidneys in eight pigs were imaged with a multiphasic contrast-enhanced fast three-dimensional sequence on a 1.5-T imager. Kidney segmentation, followed by a process of signal intensity thresholding for cortical and nephrographic phase datasets, allowed for MRI measurements of parenchymal volume and medullary fraction. Autopsy provided reference standards of renal volume, weight, and medullary fraction. RESULTS: An excellent correlation was found between MRI measurement of total renal parenchymal volume and autopsy volume (R2 = 0.86) and weight (R2 = 0.90). Medullary fraction (mean +/- SD) measured with MRI was 0.120 +/- 0.067, and with autopsy was 0.116 +/- 0.025 (t-test P = 0.84, F-test P = 0.001). CONCLUSION: MRI measurements of total renal volume are accurate. MRI measurements of medullary fraction show promise, but precision is limited when using a simple signal intensity thresholding algorithm.

Maintenance and recovery stages of postischemic acute renal failure in humans.

Postischemic injury in 38 recipients of 7-day-old cadaveric renal allografts was classified into sustained (n = 15) or recovering (n = 23) acute renal failure (ARF) according to the prevailing inulin clearance. Recipients of long-standing allografts that functioned optimally (n = 16) and living transplant donors undergoing nephrectomy (n = 10) served as functional and structural controls, respectively. A combination of physiological and morphometric techniques were used to evaluate glomerular filtration rate and its determinants 1-3 h after reperfusion and again on day 7 to elucidate the mechanism for persistent hypofiltration in ARF that is sustained. Glomerular filtration rate in the sustained ARF group on day 7 was depressed by 90% (mean +/- SD); the corresponding fall in renal plasma flow was proportionately less. Neither plasma oncotic pressure nor the single-nephron ultrafiltration coefficient differed between the sustained ARF and the control group, however. A model of glomerular ultrafiltration and a sensitivity analysis were used to compute the prevailing transcapillary hydraulic pressure gradient (DeltaP), the only remaining determinant of DeltaP. This revealed that DeltaP varied between 27 and 28 mmHg in sustained ARF and 32-38 mmHg in recovering ARF on day 7 vs. 47-54 mmHg in controls. Sustained ARF was associated with persistent tubular dilatation. We conclude that depression of DeltaP, perhaps due partially to elevated tubule pressure, is the predominant cause of hypofiltration in the maintenance stage of ARF that is sustained for 7 days.