Nomenclature of function tests

We examined the vitamin D receptor genotypes (BB, Bb and bb) defined by the BsmI restriction endonuclease in relation to biochemical indices of bone metabolism in healthy Caucasian infants. We measured the serum concentrations of the carboxy-terminal propeptide of type I procollagen (PICP) and the urinary excretion of total pyridinoline, free, total and bound deoxypyridinoline, the type I collagen N-terminal and C-terminal cross-linked telopeptides. The concentrations of the urinary indices are expressed relative to creatinine. Subjects with BB genotype had the highest mean concentrations of free, total and bound deoxypyridinoline and of the N-terminal cross-linked telopeptide (P_ANOVA = 0.0016, 0.0004, 0.0002 and 0.0053, respectively). BB boys had a higher excretion of the C-terminal cross-linked telopeptide than the other genotypes (P_ANOVA = 0.0253). In a subgroup of homozygotes aged 10 (1) months, BB subjects had the highest levels of the C-terminal cross-linked telopeptide (p=0.03), and of total deoxypyridinoline (p=0.02) and pyridinoline (p=0.06) concentrations. No significant association between the vitamin D receptor genotype and PICP was found. These data suggest that there may be a contribution of the vitamin D receptor genotype to skeletal metabolism in early childhood.     

Pelvimetry and patient acceptability compared between open 0.5-T and closed 1.5-T MR systems

Our objective was to compare maternal pelvimetry and patient acceptability between open low-field (0.5-T) and closed 1.5-T MR systems. Thirty women referred for pelvimetry (pregnant: n=15) were scanned twice in the supine position, once in the vertical open system and once in the closed system. Each patient completed a comfort and acceptability questionnaire. Pelvimetric and questionnaire data were compared between systems. Total scan time was double in the open system (7:52±1:47 vs 3:12±1:20 min). Poor image quality in the open system prevented assessment of interspinous and intertuberous diameters in one woman and all measurements in another, both pregnant, with abdominal circumferences >120 cm. The open system was much more acceptable in terms of claustrophobia and confinement (both p<0.01). Claustrophobia interrupted one closed examination. Thirty-three percent of pregnant women in both systems reported fear of fetal harm. Sixty percent of all women preferred the open system, 7% the closed system, and 33% had no preference. Limits of agreement of 3–5% from the mean for all diameters confirmed good pelvimetric reproducibility. Women's preference for open-system MR pelvimetry is feasible with abdominal circumferences ≤120 cm. Electronic Publication     

Transport of cis- and trans-4-[(18)F]fluoro-L-proline in F98 glioma cells

The transport mechanisms of cis-4-[(18)F]fluoro-L-proline (cis-FPro) and trans-4-[(18)F]fluoro-L-proline (trans-FPro) were studied in F98 rat glioma cells in comparison to the natural parent [(3)H]-L-proline. Uptake rates of cis-FPro and trans-FPro in F98 glioma cells were 50-70% lower than those of [(3)H]-L-proline. The amino transport system A inhibitor MeAIB reduced the uptake of [(3)H]-L-proline by 30% and uptake of cis-FPro by 46% while uptake of trans-FPro was not significantly changed. BCH inhibited the uptake of all tracers by 35-44%, serine by 70-90% and L-proline by 60 -80%. Absence of Na(+) reduced uptake of all tracers significantly but no further inhibitory effect could be observed which suggests a component of unspecific uptake. Radioactivity of cis- and trans-FPro in the acid precipitable fraction was < 1% after 120 min incubation time while [(3)H]-L-proline exhibited a 20% incorporation into protein. Whole body PET scans in humans demonstrated a retention of cis-FPro in the renal cortex, liver and the pancreas while trans-FPro was retained particularly in muscles. We conclude that system A amino acid transport appears to be selectively relevant for cis-FPro which may contribute to the observed differences in whole body distribution of cis-FPro and trans-FPro in humans.     

Optimization of contrast agent volume for helical CT in the diagnostic assessment of patients with severe and multiple injuries.

PURPOSE: The aim of this study was to determine the optimal amount of contrast agent for helical CT of the trunk during primary radiologic evaluation of polytraumatized patients. METHOD: Eighty-three patients with severe and multiple injuries (mean age 36.2 years) underwent standardized helical CT examination with administration of a single contrast agent bolus of iohexol (Accupaque 300) at volumes of 120, 150, and 180 ml. Image quality was estimated by two blinded radiologists using a visual analogue scale. Analysis further included density measurements in regions of interest (ROIs) placed in the ascending, descending, and abdominal aorta as well as in the liver and spleen. RESULTS: The qualitative rating of the contrast agent effect after administration of 150 and 180 ml was significantly better compared with 120 ml [odds ratio (OR) 12.05, 95% confidence interval (CI) 3.50-41.52 and OR 12.14, 95% CI 3.36-43.85, respectively]. A dose increase from 120 to 150 ml resulted in a significantly better enhancement of the abdominal aorta (p = 0.006). The highest dose of 180 ml was not associated with a diagnostic gain in the other ROIs. CONCLUSION: We recommend administration of 150 ml of iohexol as the optimal amount of contrast material for single phase bolus administration in emergency helical CT examination of the chest and abdomen.     

Flow diversion treatment: intra-aneurismal blood flow velocity and WSS reduction are parameters to predict aneurysm thrombosis

Background

To evaluate the haemodynamic changes induced by flow diversion treatment in cerebral aneurysms, resulting in thrombosis or persisting aneurysm patency over time.

Method

Eight patients with aneurysms at the para-ophthalmic segment of the internal carotid artery were treated by flow diversion only. The clinical follow-up ranged between 6?days and 12?months. Computational fluid dynamics (CFD) analysis of pre- and post-treatment conditions was performed in all cases. True geometric models of the flow diverter were created and placed over the neck of the aneurysms by using a virtual stent-deployment technique, and the device was simulated as a true physical barrier. Pre- and post-treatment haemodynamics were compared, including mean and maximal velocities, wall-shear stress (WSS) and intra-aneurysmal flow patterns. The CFD study results were then correlated to angiographic follow-up studies.

Results

Mean intra-aneurysmal flow velocities and WSS were significantly reduced in all aneurysms. Changes in flow patterns were recorded in only one case. Seven of eight aneurysms showed complete occlusion during the follow-up. One aneurysm remaining patent after 1?year showed no change in flow patterns. One aneurysm rupturing 5?days after treatment showed also no change in flow pattern, and no change in the maximal inflow velocity.

Conclusions

Relative flow velocity and WSS reduction in and of itself may result in aneurysm thrombosis in the majority of cases. Flow reductions under aneurysm–specific thresholds may, however, be the reason why some aneurysms remain completely or partially patent after flow diversion.     

Adult patients with sporadic polycystic kidney disease: the importance of screening for mutations in the PKD1 and PKD2 genes

Background

ADPKD is one of the most common inherited disorders, with high risk for end-stage renal disease. Numerous patients, however, have no relatives in whom this disorder is known and are unsure whether they may transmit the disease to their offsprings. The aim of this study was to evaluate whether germline mutation analysis adds substantial information to clinical symptoms for diagnosis of ADPKD in these patients.

Methods

Clinical data included renal function and presence of liver or pancreas cysts, heart valve insufficiency, intracranial aneurysms, colonic diverticles, and abdominal hernias. Family history was evaluated regarding ADPKD. Germline mutation screening of the PKD1 and PKD2 genes was performed for intragenic mutations and for large deletions.

Results

A total of 324 adult patients with ADPKD including 30 patients without a family history of ADPKD (sporadic cases) were included. PKD1 mutations were found in 24/30 and PKD2 mutations in 6 patients. Liver cysts were present in 14 patients and intracranial aneurysms in 2 patients. Fourteen patients (45%) had no extrarenal involvement. Compared to the 294 patients with familial ADPKD, the clinical characteristics and the age at the start of dialysis were similar in those with sporadic ADPKD.

Conclusion

The clinical characteristics of patients with sporadic and familial ADPKD are similar, but sporadic ADPKD is often overlooked because of the absence of a family history. Molecular genetic screening for germline mutations in both PKD1 and PKD2 genes is essential for the definitive diagnosis of ADPKD.     

[18F]Fluciclatide in the in vivo evaluation of human melanoma and renal tumors expressing αvβ3 and αvβ5 integrins

Purpose

[¹⁸F]Fluciclatide is an integrin-targeted PET radiopharmaceutical. α_vβ₃ and α_vβ₅ are upregulated in tumor angiogenesis as well as on some tumor cell surfaces. Our aim was to use [¹⁸F]fluciclatide (formerly known as [¹⁸F]AH111585) for PET imaging of angiogenesis in melanoma and renal tumors and compare with tumor integrin expression.

Methods

Eighteen evaluable patients with solid tumors ≥2.0 cm underwent [¹⁸F]fluciclatide PET/CT. All patients underwent surgery and tumor tissue samples were obtained. Immunohistochemical (IHC) staining with mouse monoclonal antibodies and diaminobenzidine (DAB) was applied to snap-frozen tumor specimens, and additional IHC was done on formalin-fixed paraffin-embedded samples. DAB optical density (OD) data from digitized whole-tissue sections were compared with PET SUV_{80% max}, and Patlak influx rate constant (K _i) data, tumor by tumor.

Results

Tumors from all 18 patients demonstrated measurable [¹⁸F]fluciclatide uptake. At the final dynamic time-point (55 min after injection), renal malignancies (in 11 patients) demonstrated an average SUV_{80% max} of 6.4?±?2.0 (range 3.8 – 10.0), while the average SUV_{80% max} for metastatic melanoma lesions (in 6 patients) was 3.0?±?2.0 (range 0.7 – 6.5). There was a statistically significant difference in [¹⁸F]fluciclatide uptake between chromophobe and nonchromophobe renal cell carcinoma (RCCs, with SUV_{80% max} of 8.2?±?1.8 and 5.4?±?1.4 (P?=?0.020) and tumor-to-normal kidney (T/N) ratios of 1.5?±?0.4 and 0.9?±?0.2, respectively (P?=?0.029). The highest Pearson's correlation coefficients were obtained when comparing Patlak K _i and α_vβ₅ OD when segregating the patient population between melanoma and RCC (r?=?0.83 for K _i vs. melanoma and r?=?0.91 for K _i vs. RCC). SUV_{80% max} showed a moderate correlation with α_vβ₅ and α_vβ₃ OD.

Conclusion

[¹⁸F]Fluciclatide PET imaging was well tolerated and demonstrated favorable characteristics for imaging α_vβ₃ and α_vβ₅ expression in melanoma and RCC. Higher uptake was observed in chromophobe than in nonchromophobe RCC. [¹⁸F]Fluciclatide may be a useful radiotracer to improve knowledge of integrin expression.