Cyclosporine A does not alter ultrasonic indices of renal blood flow: a potential tool for differentiating toxicity from acute rejection?

The narrow therapeutic window of cyclosporine A (CsA) means its use is controlled by pharmacokinetic monitoring. However, pharmacokinetics do not always reflect the functional effects of a drug--its pharmacodynamics, such as vasoconstriction. We developed a technique for measuring renal blood flow and used a pig model to determine whether CsA-induced renal vasoconstriction could be detected, thus offering a tool for pharmacodynamic therapeutic drug monitoring. This has been shown to differentiate acute rejection from acute tubular necrosis. Power Doppler intensitometry was used to assess relative vascular volume, and the renal arteriovenous transit time was determined with an intravenous microbubble bolus. Measurements were taken before and at intervals after an intravenous bolus of CsA (10 mg/kg). There was no correlation between index and CsA concentration. Lack of detectable effect after CsA administration to high concentrations suggests that this technique may be able to differentiate CsA toxicity from acute rejection.

Improved characterization of liver lesions with liver-phase uptake of liver-specific microbubbles: prospective multicenter study.

PURPOSE: To evaluate in a prospective multicenter study whether conventional ultrasonographic (US) characterization of liver lesions can be improved by imaging during the liver-specific phase of SH U 508A uptake in the microbubble-specific agent detection imaging mode. MATERIALS AND METHODS: One hundred forty-two patients with liver lesions underwent conventional gray-scale and color Doppler US and SH U 508A-enhanced US. Two radiologists blindly read digital cine clips and assigned scores for confidence in diagnosis of benignancy or malignancy, diagnosis of specific lesion types, and relative difference in SH U 508A uptake between the lesion and the liver parenchyma (ie, subjective conspicuity score [SCS]). Comparisons were made to see whether the addition of agent detection imaging led to improved diagnostic performance. RESULTS: Receiver operating characteristic analysis revealed improved discrimination of benign and malignant lesions for readers 1 (P =.049) and 2 (P <.001). The number of patients with a correct diagnosis of benignancy or malignancy assigned by readers 1 and 2, respectively, improved from 114 and 113 to 125 and 128 with agent detection imaging (reader 1: P =.027; reader 2: P =.008; McNemar test). Specific diagnoses were made more accurately with agent detection imaging: At McNemar testing, the number of correct lesion type determinations increased from 83 to 92 (P =.022) for reader 1 and from 85 to 99 (P <.001) for reader 2. Both readers assigned high scores for differences in SH U 508A uptake between the liver parenchyma and the lesion for metastases and cholangiocarcinomas and low scores for uptake differences in most of the benign lesions. Hepatocellular carcinomas (HCCs), hemangiomas, and adenomas had more variable uptake differences. Fourteen of 22 hemangiomas were assigned an SCS of less than 50%, and 22 (reader 1) and 15 (reader 2) of 31 HCCs were assigned an SCS of greater than 50%. CONCLUSION: With use of SH U 508A-enhanced agent detection imaging, liver lesion characterization and diagnostic performance are significantly improved.