Perhexiline maleate in the treatment of fibrodysplasia ossificans progressiva: an open-labeled clinical trial.

BACKGROUND: Currently, there are no effective medical treatment options to prevent the formation of heterotopic bones in fibrodysplasia ossificans progressiva (FOP). By the drug repositioning strategy, we confirmed that perhexiline maleate (Pex) potentially ameliorates heterotopic ossification in model cells and mice. Here, we conducted a prospective study to assess the efficacy and safety of Pex in the treatment of FOP patients. METHODS: FOP patients in this open-label single-center study were treated with Pex for a total of 12 months, and followed up for 12 consecutive months after medication discontinuation. The safety of the treatment was assessed regularly by physical and blood examinations. The efficacy of Pex for preventing heterotopic ossifications was evaluated by the presence of flare-ups, measurements of serum bone markers, and changes in the total bone volume calculated by the three-dimensional computed tomography (3D-CT) images. RESULTS: Five patients with an average age of 23.4 years were enrolled. Within safe doses of Pex administration in each individual, there were no drug-induced adverse effects during the medication phase. Three patients showed no intense inflammatory reactions during the study period, while two patients had acute flare-ups around the hip joint without evidence of trauma during the medication phase. In addition, one of them became progressively incapable of opening her mouth over the discontinuation phase. Serum levels of alkaline phosphatase (ALP) and bone specific ALP (BAP) were significantly and synchronously increased with the occurrence of flare-ups. Volumetric 3D-CT analysis demonstrated a significant increase in the total bone volume of Case 2 (378 cm(3)) and Case 3 (833 cm(3)) during the two-year study period. CONCLUSIONS: We could not prove the efficacy of oral Pex administration in the prevention of heterotopic ossifications in FOP. Serum levels of ALP and BAP appear to be promising biomarkers for monitoring the development of ectopic ossifications and efficacy of the therapy. Quantification of change in the total bone volume by whole body CT scanning could be a reliable evaluation tool for disease progression in forthcoming clinical trials of FOP.

Organ and effective dose evaluation in diagnostic radiology based on in-phantom dose measurements with novel photodiode-dosemeters.

Organ and the effective doses of patients undergoing clinical X ray examinations of chest and abdomen were evaluated with an anthropomorphic phantom and a new dosimetry system. The system was comprised of 34 pin photodiode dosemeters placed in/on particular tissues or organs of the anthropomorphic phantom, where the tissues and organs are defined by the International Commission on Radiological Protection (ICRP) to estimate the effective doses. Dosemeter signals were acquired on a personal computer directly, and converted into absorbed doses, from which the organ and the effective doses were evaluated on the computer. Our study showed that organ doses ranged from <0.01 to 0.72 mGy in routine X-ray radiography of chest and of abdomen and from 0.07 to 55.91 mGy in routine computed tomography (CT) examinations with current multi-slice CT scanners. The effective dose observed in the chest CT examination was approximately 300 times higher than that in chest radiography.

Multiphase contrast-enhanced CT of the liver with a multislice CT scanner: effects of iodine concentration and delivery rate.

PURPOSE: To determine whether or not high-concentration contrast material is useful in multiphase contrast-enhanced CT of the liver with a multislice CT scanner. MATERIALS AND METHODS: One hundred twenty-four examinations, in which first- and second-pass acquisitions (double arterial phase imaging) were performed during a single breath-hold followed by third-pass acquisition, were randomized into three protocols: contrast injection at 0.07 mL/kg body weight/sec over 30 sec at an iodine concentration of 300 mgI/mL in group 1, contrast injection at 0.06 mL/kg body weight/sec over 30 sec at an iodine concentration of 350 mgI/mL in group 2, and contrast injection at 0.07 mL/kg body weight/sec over 25.7 sec at an iodine concentration of 350 mgI/mL in group 3. Each group received an equivalent iodine dose per kg body weight (2.1 mL/kg of contrast material of 300 mgI/mL). Contrast enhancement in each acquisition was measured in the aorta, portal vein, and liver. RESULTS: No statistically significant differences were seen between groups 1 and 2 in any enhancement in any acquisition. In group 3, aortic enhancement in the first-pass acquisition was significantly more intense than in groups 1 and 2, while portal venous enhancement and hepatic enhancement were equivalent. CONCLUSION: Shortening the injection duration for a given iodine dose with high-concentration contrast material (group 3) can achieve improved arterial enhancement on arterial phase images.

Late-arterial and portal-venous phase imaging of the liver with a multislice CT scanner in patients without circulatory disturbances: automatic bolus tracking or empirical scan delay?

The value of automatic bolus tracking in late-arterial and portal-venous phase imaging of the liver with a multislice CT scanner as compared with fixed time-delay examination in patients without circulatory disturbances is evaluated. For the evaluation of known or suspected liver disease, 98 multiphase contrast-enhanced CT examinations including double late-arterial phase imaging were randomized into either scanning with a scan delay of 30 s from the beginning of contrast material injection or scanning with automatic bolus tracking. Contrast material was injected at 0.07 ml/kg body weight/s over 30 s. Contrast enhancement in each acquisition was measured in the aorta, portal vein, liver, pancreas and hepatocellular carcinomas. The density difference between hepatocellular carcinomas and the hepatic parenchyma was calculated. The mean time to the first-pass acquisition as determined by automatic bolus tracking was 29.6 s. No statistically significant difference was observed between the two groups either in any enhancement in any acquisition or in the lesion-to-liver density difference. The use of automatic bolus tracking in late-arterial and portal-venous phase hepatic CT does not significantly improve the degree of contrast enhancement in the aorta, portal vein, liver and pancreas or lesion-to-liver conspicuity in patients without circulatory disturbances.

Multiphase contrast-enhanced CT of the liver with a multislice CT scanner.

Our objective was to assess the effects of the injection rate of contrast material and of a 5% dextrose flush on enhancement in multiphase hepatic CT using a multislice CT scanner. Most patients had chronic hepatitis and/or liver cirrhosis. One hundred eighty examinations, in which two sequential acquisitions were performed during a single breath-hold followed by third- and fourth-pass acquisitions, were randomized into four protocols: contrast injection at 0.1 ml/kg body weight s(-1) over 21 s without and with a 30-ml flush in groups 1 and 2, respectively, and contrast injection at 0.07 ml/kg body weight s(-1) over 30 s without and with a flush in groups 3 and 4, respectively. Contrast enhancement in each acquisition was measured in the aorta, portal vein, and liver. The visualization of hepatic arterial branches was scored by visual assessment. The highest aortic enhancement was observed in the first-pass acquisition in all groups. At the higher injection rate (groups 1 and 2), aortic enhancement in the first-pass acquisition was significantly more intense, whereas portal venous and hepatic enhancement was significantly less intense. The use of a flush considerably improved aortic enhancement at the beginning of the second-pass acquisition. In the visual assessment of hepatic arterial branches, the protocols with the higher injection rate received significantly higher grades. Multislice CT permits the entire liver to be imaged during an almost exclusively arterial phase by shortening the injection duration for a given volume of contrast material.