Heterogeneity of pulmonary perfusion as a mechanistic image-based phenotype in emphysema susceptible smokers.

Recent evidence suggests that endothelial dysfunction and pathology of pulmonary vascular responses may serve as a precursor to smoking-associated emphysema. Although it is known that emphysematous destruction leads to vasculature changes, less is known about early regional vascular dysfunction which may contribute to and precede emphysematous changes. We sought to test the hypothesis, via multidetector row CT (MDCT) perfusion imaging, that smokers showing early signs of emphysema susceptibility have a greater heterogeneity in regional perfusion parameters than emphysema-free smokers and persons who had never smoked (NS). Assuming that all smokers have a consistent inflammatory response, increased perfusion heterogeneity in emphysema-susceptible smokers would be consistent with the notion that these subjects may have the inability to block hypoxic vasoconstriction in patchy, small regions of inflammation. Dynamic ECG-gated MDCT perfusion scans with a central bolus injection of contrast were acquired in 17 NS, 12 smokers with normal CT imaging studies (SNI), and 12 smokers with subtle CT findings of centrilobular emphysema (SCE). All subjects had normal spirometry. Quantitative image analysis determined regional perfusion parameters, pulmonary blood flow (PBF), and mean transit time (MTT). Mean and coefficient of variation were calculated, and statistical differences were assessed with one-way ANOVA. MDCT-based MTT and PBF measurements demonstrate globally increased heterogeneity in SCE subjects compared with NS and SNI subjects but demonstrate similarity between NS and SNI subjects. These findings demonstrate a functional lung-imaging measure that provides a more mechanistically oriented phenotype that differentiates smokers with and without evidence of emphysema susceptibility.

Topomorphologic separation of fused isointensity objects via multiscale opening: separating arteries and veins in 3-D pulmonary CT.

A novel multiscale topomorphologic approach for opening of two isointensity objects fused at different locations and scales is presented and applied to separating arterial and venous trees in 3-D pulmonary multidetector X-ray computed tomography (CT) images. Initialized with seeds, the two isointensity objects (arteries and veins) grow iteratively while maintaining their spatial exclusiveness and eventually form two mutually disjoint objects at convergence. The method is intended to solve the following two fundamental challenges: how to find local size of morphological operators and how to trace continuity of locally separated regions. These challenges are met by combining fuzzy distance transform (FDT), a morphologic feature with a topologic fuzzy connectivity, and a new morphological reconstruction step to iteratively open finer and finer details starting at large scales and progressing toward smaller scales. The method employs efficient user intervention at locations where local morphological separability assumption does not hold due to imaging ambiguities or any other reason. The approach has been validated on mathematically generated tubular objects and applied to clinical pulmonary noncontrast CT data for separating arteries and veins. The tradeoff between accuracy and the required user intervention for the method has been quantitatively examined by comparing with manual outlining. The experimental study, based on a blind seed selection strategy, has demonstrated that above 95% accuracy may be achieved using 25-40 seeds for each of arteries and veins. Our method is very promising for semiautomated separation of arteries and veins in pulmonary CT images even when there is no object-specific intensity variation at conjoining locations.

Noninvasive assessment of early kidney allograft dysfunction by blood oxygen level-dependent magnetic resonance imaging.

BACKGROUND: Blood oxygen level-dependent (BOLD) magnetic resonance imaging (MRI) is a noninvasive method to assess tissue oxygen bioavailability, using deoxyhemoglobin as an endogenous contrast agent. We hypothesized that BOLD-MRI could accurately discriminate different types of rejection early after kidney transplantation. METHODS: Twenty-three patients underwent imaging in the first four months posttransplant. Five had normal functioning transplants and 18 had biopsy-proven acute allograft dysfunction (acute tubular necrosis [ATN, n=5] and acute rejection [n=13] including borderline rejection: n=3; IA rejection: n=4; IIA rejection: n=6: C4d(+) rejection: n=9). RESULTS: Mean medullary R2* (MR2*) levels (a measure directly proportional to tissue deoxyhemoglobin levels) were significantly higher in normal functioning allografts (R2*=24.3/s+/-2.3) versus acute rejection (R2*=16.6/s+/-2.1) and ATN (R2*=20.9/s+/-1.8) (P<0.05). The lowest MR2* levels were observed in acute rejection episodes with vascular injury i.e. IIA and C4d (+). Similarly, the lowest medullary to cortical R2* ratios (MCR2*) were present in allografts with IIA (1.24+/-0.05) and C4d(+) rejection (1.26+/-0.06). ROC curve analyses suggested that MR2* and MCR2* values could accurately discriminate acute rejection in the early posttransplant period. CONCLUSIONS: BOLD-MRI demonstrated significant changes in medullary oxygen bioavailability in allografts with biopsy-proven ATN and acute rejection, suggesting that there may be a role for this noninvasive tool to evaluate kidney function early after transplantation.

Assessment of acute renal transplant rejection with blood oxygen level-dependent MR imaging: initial experience.

PURPOSE: To prospectively assess the oxygenation state of renal transplants and determine the feasibility of using blood oxygen level-dependent (BOLD) magnetic resonance (MR) imaging to differentiate between acute tubular necrosis (ATN), acute rejection, and normal function. MATERIALS AND METHODS: This HIPAA-compliant study had institutional human subjects review committee approval, and written informed consent was obtained from all patients. BOLD MR imaging was performed in 20 patients (age range, 21-70 years) who had recently received renal transplants. Six patients had clinically normal functioning transplants, eight had biopsy-proved rejection, and six had biopsy-proved ATN. R2* (1/sec) measurements were obtained in the medulla and cortex of transplanted kidneys. R2* is a measure of the rate of signal loss in a specific region and is related to the amount of deoxyhemoglobin present. Statistical analysis was performed by using a two-sample t test. Threshold R2* values were identified to discriminate between transplanted kidneys with ATN, those with acute rejection, and those with normal function. RESULTS: R2* values for the medulla were significantly lower in the acute rejection group (R2* = 15.8/sec +/- 1.5) than in normally functioning transplants (R2* = 23.9/sec +/- 3.2) and transplants with ATN (R2* = 21.3/sec +/- 1.9). The differences between the acute rejection and normal function groups (P = .001), as well as between the acute rejection and ATN groups (P < .001), were significant. Acute rejection could be differentiated from normal function and ATN in all cases by using a threshold R2* value of 18/sec. R2* values for the cortex were higher in ATN (R2* = 14.2/sec +/- 1.4) than for normally functioning transplants (R2* = 12.7/sec +/- 1.6) and transplants with rejection (R2* = 12.4/sec +/- 1.2). The difference in R2* values in the cortex between ATN and rejection was statistically significant (P = .034), although there was no threshold value that enabled differentiation of all cases of ATN from cases of normal function or acute rejection. CONCLUSION: R2* measurements in the medullary regions of transplanted kidneys with acute rejection were significantly lower than those in normally functioning transplants or transplants with ATN. These results suggest that marked changes in intrarenal oxygenation occur during acute transplant rejection.

Detection of acute renal ischemia in swine using blood oxygen level-dependent magnetic resonance imaging.

PURPOSE: To determine the feasibility and sensitivity of blood oxygen level-dependent (BOLD) magnetic resonance imaging (MRI) to detect acute renal ischemia, using a swine model, and to present the causes of variability and assess techniques that minimize variability introduced during data analysis. MATERIALS AND METHODS: BOLD MRI was performed in axial and coronal planes of the kidneys of five swine. Color R2* maps were calculated and mean R2* values and 95% confidence intervals (CIs) for the cortex and medulla were determined for baseline, renal artery occlusion and reperfusion conditions. Paired Student's t-tests were used to determine significance. RESULTS: Mean R2* measurements increased from baseline during renal artery occlusion in the cortex (axial, 13.8-24.6 second(-1); coronal, 14.4-24.7 second(-1)) and medulla (axial, 19.3-32.2 second(-1); coronal, 20.1-30.7 second(-1)). These differences were significant for both the cortex (axial, P < 0.04; coronal, P < 0.005) and medulla (axial, P < 0.02; coronal, P < 0.0005). No significant change was observed in the contralateral kidney. CONCLUSION: R2* values were significantly higher than baseline for medulla and cortex during renal artery occlusion. More variability exists in R2* measurements in the medulla than the cortex and in the axial than the coronal plane.