Warner, Lizette

Functional renal oxygen consumption, V r O 2 is due to tubular reabsorption of sodium (T Na ) in the proximal and distal nephrons, resulting in compartments (cortex/medulla) with distinct V r O 2 /T Na relationships. Compartmental divisions promote non‐invasive imaging strategies like MRI, to indirectly assess tissue oxygenation, (P t O 2 ). However, the extent to which these regional P t O 2 differences are affected by successive T Na are not fully understood. The objective is to determine V r O 2 and intra‐renal regional alterations in P t O 2 directly and indirectly during successive T Na inhibition. It is hypothesized successive T Na inhibition is accompanied by intra‐renal regional changes in P t O 2 . Pigs (n=6) underwent MRI scans at baseline, furosemide and acetazolamide. Five days later, the right kidney was instrumented with P t O 2 sensors (cortex/medulla). P t O 2 was measured during drug infusions (identical to MRI exam). There was a decrease in V r O 2 , and a 40% and 30% increase in medullary and cortical P t O 2 following drug infusions. There was ~25% medullary and ~20–30% cortical decrease in BOLD signal with furosemide and acetazolamide administration, respectively. This study suggests successive inhibition of T Na is accompanied by intra‐renal regional P t O 2 changes and these changes are detectable with BOLD‐MRI, a non‐invasive imaging modality. Funding provided by NIH Grant (HL16496‐32), 2007 APS Porter Physiology Fellowship and the Mayo Foundation.

Functional renal oxygen consumption, V r O 2 is due to tubular reabsorption of sodium (T Na ) in the proximal (∼67%) and distal(∼30%) nephrons, resulting in compartments (cortex/medulla) with distinct V r O 2 /T Na relationships. A progressive drop in renal blood flow (RBF) with renal arterial stenosis (RAS), disrupts O 2 delivery, vital for reabsorption. The overall objective for the study is to determine the intra‐renal regional alterations in tissue oxygenation (P t O 2 ) and theV r O 2 /T Na relationship in acute RAS. The hypothesis is RAS is accompanied by intra‐renal regional changes in oxygenation. Unilateral acute RAS was induced in 8 pigs by an extra‐vascular balloon. RBF and P t O 2 were measured continuously with an ultrasound flow probe during baseline, RBF autoregulation and 3 sequential decreases in RBF, recovery, and furosemide administration. V r O 2 was determined using Fick arterio‐venous differences. There were concomitant decreases in V r O 2 , and P t O 2 throughout the occlusion periods. Medullary P t O 2 changes were 35% more pronounced than cortical. This study suggests medullary decreases in P t O 2 are more aggravated than cortical changes with reductions in RBF, accentuating the medulla's vulnerability to progressive RAS. Mild to moderately severe obstructions seem to preserve the tubular transport costs. Funding provided by NIH Grant (HL16496‐32), 2007 APS Porter Physiology Fellowship and the Mayo Foundation.

Renal artery stenosis (RAS) may lead to hypertension and renal injury. Reversibility of renal tubular dysfunction in RAS upon revascularization is unclear. We tested the hypothesis that percutaneous transluminal renal angioplasty (PTRA) would restore tubular function assessed as medullary oxygenation response to furosemide, a diuretic that inhibits medullary tubular transport. This was studied in 16 pigs after 6 wks of RAS, using blood oxygen level dependent magnetic resonance imaging (BOLD MRI) before and after furosemide. Renal blood flow (RBF) and glomerular filtration rate (GFR) were determined with multidetector computed tomography. Pigs were then randomized for PTRA or sham (n=8 each) and studied again 4 wks later; 8 normal pigs served as controls. Results Stenotic kidney RBF, GFR, and BOLD MRI responses were reduced in RAS shams (Figure). PTRA decreased the degree of stenosis (11±7 vs. 71±5% in untreated RAS) and blood pressure (108±3 vs. 130±9 mmHg, p<0.05). Renal and tubular function were improved in RAS+PTRA, although not to normal (Figure). Non‐stenotic kidneys showed no change in tubular function. Therefore, tubular solute transport‐related oxygen consumption can be partially restored and detected by BOLD MRI 4 wks after PTRA in post stenotic swine kidneys. This noninvasive method may be useful to assess the functional status of kidneys in RAS patients. Supported by NIH, HL085307.

PurposeA magnetic resonance (MR) biologic marker (biomarker) is a measurable quantitative characteristic that is an indicator of normal biological and pathogenetic processes or a response to therapeutic intervention derived from the MR imaging process. There is significant potential for MR biomarkers to facilitate personalized approaches to cancer care through more precise disease targeting by quantifying normal versus pathologic tissue function as well as toxicity to both radiation and chemotherapy. Both of which have the potential to increase the therapeutic ratio and provide earlier, more accurate monitoring of treatment response. The ongoing integration of MR into routine clinical radiation therapy (RT) planning and the development of MR guided radiation therapy systems is providing new opportunities for MR biomarkers to personalize and improve clinical outcomes. Their appropriate use, however, must be based on knowledge of the physical origin of the biomarker signal, the relationship to the underlying biological processes, and their strengths and limitations. The purpose of this report is to provide an educational resource describing MR biomarkers, the techniques used to quantify them, their strengths and weakness within the context of their application to radiation oncology so as to ensure their appropriate use and application within this field.

Blood oxygen level-dependent (BOLD) MRI data of kidney, while indicative of tissue oxygenation level (Po2), is in fact influenced by multiple confounding factors, such as R2, perfusion, oxygen permeability, and hematocrit. We aim to explore the feasibility of extracting tissue Po2 from renal BOLD data. A method of two steps was proposed: first, a Monte Carlo simulation to estimate blood oxygen saturation (SHb) from BOLD signals, and second, an oxygen transit model to convert SHb to tissue Po2. The proposed method was calibrated and validated with 20 pigs (12 before and after furosemide injection) in which BOLD-derived tissue Po2 was compared with microprobe-measured values. The method was then applied to nine healthy human subjects (age: 25.7 ± 3.0 yr) in whom BOLD was performed before and after furosemide. For the 12 pigs before furosemide injection, the proposed model estimated renal tissue Po2 with errors of 2.3 ± 5.2 mmHg (5.8 ± 13.4%) in cortex and −0.1 ± 4.5 mmHg (1.7 ± 18.1%) in medulla, compared with microprobe measurements. After injection of furosemide, the estimation errors were 6.9 ± 3.9 mmHg (14.2 ± 8.4%) for cortex and 2.6 ± 4.0 mmHg (7.7 ± 11.5%) for medulla. In the human subjects, BOLD-derived medullary Po2 increased from 16.0 ± 4.9 mmHg (SHb: 31 ± 11%) at baseline to 26.2 ± 3.1 mmHg (SHb: 53 ± 6%) at 5 min after furosemide injection, while cortical Po2 did not change significantly at ∼58 mmHg (SHb: 92 ± 1%). Our proposed method, validated with a porcine model, appears promising for estimating tissue Po2 from renal BOLD MRI data in human subjects.

Oxygen consumption beyond the proximal tubule is mainly determined by active solute reabsorption, especially in the thick ascending limb of the Loop of Henle. Furosemide-induced suppression of oxygen consumption (FSOC) involves inhibition of sodium transport in this segment, which is normally accompanied by a marked decrease in the intrarenal deoxyhemoglobin detectable by blood oxygen level-dependent (BOLD)-magnetic resonance imaging (MRI). This study tested the hypothesis that the magnitude of BOLD-MRI signal change after furosemide is related to impaired renal function in renovascular hypertension. In 16 pigs with unilateral renal artery stenosis, renal hemodynamics, function, and tubular function (FSOC and fluid concentration capacity) were evaluated in both kidneys using MR and multidetector computerized tomography (MDCT) imaging. Animals with adequate FSOC (23.6 ± 2.2%, P > 0.05 vs. baseline) exhibited a mean arterial pressure (MAP) of 113 ± 7 mmHg, and relatively preserved glomerular filtration rate (GFR) of 60 ± 4.5 ml/min, comparable to their contralateral kidney (66 ± 4 ml/min, P > 0.05). In contrast, animals with low FSOC (3.1 ± 2.1%, P = NS vs. baseline) had MAP of 124 ± 9 mmHg and GFR (22 ± 6 ml/min) significantly lower than the contralateral kidneys (66 ± 4 ml/min, P < 0.05). The group with preserved GFR and FSOC showed an increase in intratubular fluid concentration as assessed by MDCT that was greater than that observed in the low GFR group, suggesting better preservation of tubular function in the former group. These results suggest that changes in BOLD-MRI after furosemide can differentiate between underperfused kidneys with preserved tubular function and those with tubular dysfunction. This approach may allow more detailed physiologic evaluation of poststenotic kidneys in renovascular hypertension than previously possible.