Test-retest reproducibility of 18F-MPPF PET in healthy humans: a reliability study.

The aim of this study was to assess the reliability of 2'-methoxyphenyl-(N-2'-pyridinyl)-p-18F-fluoro-benzamidoethylpiperazine (18F-MPPF) PET binding parameter's quantification via a test-retest study over a long-term period. METHODS: Ten healthy volunteers underwent 2 dynamic 18F-MPPF PET scans in an interval of 6 mo. As a methodologic control, 10 simulated datasets, including interindividual functional and anatomic variabilities, were also used to assess the measurement variations in the absence of intraindividual variability. Indices of tracer binding were computed using 2 different models: (a) the simplified reference tissue model (SRTM) and (b) the Logan graphical model. The SRTM allows computing the binding potential (BP) index and plasma-to-brain transport constants (R1, k2). The Logan model evaluates the distribution volume (DV). For both methods, cerebellum was taken as the reference region. From both models, binding indices were calculated with time-activity curves extracted from regions of interest, on one hand, and for each voxel to perform parametric images on the other hand. RESULTS: Reliability indices--that is, bias, variability, and intraclass correlation (ICC)--indicated a good reproducibility: the BP percentage change in mean between test and retest is close to 1% in rich regions and 2% in poor regions. The typical error is around 7%. Mean ICC is over 0.70. The DV percentage change in the mean is +/-2.5%, with a typical error close to 6% and an ICC over 0.60. CONCLUSION: Our results show a good reliability, with a reasonable level of intraindividual biologic variability that allows crossover studies with 18F-MPPF in which small percentage changes are expected between test and retest measurements, in group studies and for single subject assessment.     

Coronary artery motion and cardiac phases: dependency on heart rate -- implications for CT image reconstruction

This study had institutional review board approval; written informed consent was obtained. The purpose was to prospectively determine the heart rate (HR) dependency of three-dimensional (3D) coronary artery motion by incorporating into analysis the durations of systole and diastole. Thirty patients (seven women, 23 men; mean age, 56.6 years +/- 12.7 [standard deviation]; HR: 45-100 beats per minute) underwent electrocardiographically gated 64-section computed tomographic (CT) coronary angiography to determine coronary motion velocities at bifurcation points. Significance of velocity differences (P < .05) was determined by using analysis of variance for repeated measures and Bonferroni post hoc tests. HR dependency was determined by using linear regression analysis. HR significantly affected 3D coronary motion (r = 0.47, P < .009) through nonproportional shortening of systole and diastole (r = -0.82, P < .001), leading to percentage reconstruction interval shifts of coronary velocity troughs and peaks (P < .01). Results suggest that image reconstruction algorithms at CT coronary angiography be adapted to the individual patient's HR.     

Rheological Changes After Stenting of a Cerebral Aneurysm: A Finite Element Modeling Approach

Hemodynamic changes in intracranial aneurysms after stent placement include the appearance of areas with stagnant flow and low shear rates. We investigated the influence of stent placement on blood flow velocity and wall shear stress of an intracranial aneurysm using a finite element modeling approach. To assess viscosity changes induced by stent placement, the rheology of blood as non-Newtonian fluid was taken into account in this model. A two-dimensional model with a parent artery, a smaller branching artery, and an aneurysm located at the bifurcation, before and after stent placement, was used for simulation. Flow velocity plots and wall shear stress before and after stent placement was calculated over the entire cardiac circle. Values for dynamic viscosity were calculated with a constitutive equation that was based on experimental studies and yielded a viscosity, which decreases as the shear rate increases. Stent placement lowered peak velocities in the main vortex of the aneurysm by a factor of at least 4 compared to peak velocities in the main artery, and it considerably decreased the wall shear stress of the aneurysm. Dynamic viscosity increases after stent placement persisted over a major part of the cardiac cycle, with a factor of up to 10, most pronounced near the dome of the aneurysm. Finite element modeling can offer insight into rheological changes induced by stent treatment of aneurysms and allows visualizing dynamic viscosity changes induced by stent placement.     

Radiolabelled monoclonal antibodies against alpha-fetoprotein for in vivo localization of human hepatocellular carcinoma by immunotomoscintigraphy

Two high affinity monoclonal antibodies, designated AF01 and AF04, directed against distinct epitopes of human alpha-fetoprotein (AFP) and the Fab fragments of one of them, were labelled with ¹³¹I and injected into 18 patients with AFP producing hepatocellular carcinoma (HCC) in order to carry out imaging studies by tomoscintigraphy. Twelve patients were injected with whole antibody, only three of seven patients injected with AF01 and two of five patients injected with AF04 had a positive scan. In contrast, five out of six patients injected with labelled Fab fragments of AF04 had positive imaging. These results confirm that tumour imaging of HCC using ¹³¹I labelled monoclonal antibody against AFP is feasible. Moreover, utilization of tomoscintigraphy in place of linear scintigraphy and Fab fragments instead of whole immunoglobulin may improve the sensitivity of radioimmunolocalization. This technique provides useful information on the in vivo distribution of monoclonal antibodies directed against AFP and on the practicability of the eventual therapeutic use of anti-AFP antibodies in HCC.This work was supported by Grant number 84D16 from the Institut Gustave-Roussy     

Ischemic preconditioning for major liver resection under vascular exclusion of the liver preserving the caval flow: a randomized prospective study

BACKGROUND: Two randomized prospective studies suggested that ischemic preconditioning (IP) protects the human liver against ischemia-reperfusion injury after hepatectomy performed under continuous clamping of the portal triad. The primary goal of this study was to determine whether IP protects the human liver against ischemia-reperfusion injury after hepatectomy under continuous vascular exclusion with preservation of the caval flow. STUDY DESIGN: Sixty patients were randomly divided into two groups: with (n=30; preconditioning group) and without (n=30; control group) IP (10 minutes of portal triad clamping and 10 minutes of reperfusion) before major hepatectomy under vascular exclusion of the liver preserving the caval flow. Serum concentrations of aspartate transferase, alanine transferase, glutathione-S-transferase, and bilirubin and prothrombin time were regularly determined until discharge and at 1 month. Morbidity and mortality were determined in both groups. RESULTS: Peak postoperative concentrations of aspartate transferase were similar in the groups with and without IP (851 +/- 1,733 IU/L and 427 +/- 166 IU/L respectively, p=0.2). A similar trend toward a higher peak concentration of alanine transferase and glutathione-S-transferase was indeed observed in the preconditioning group compared with the control group. Morbidity and mortality rates and lengths of ICU and hospitalization stays were similar in both groups. CONCLUSIONS: IP does not improve liver tolerance to ischemia-reperfusion after hepatectomy under vascular exclusion of the liver with preservation of the caval flow. This maneuver does not improve postoperative liver function and does not affect morbidity or mortality rates. The clinical use of IP through 10 minutes of warm ischemia in this technique of hepatectomy is not currently recommended.     

Monitoring Treatment Response and Metastatic Relapse in Advanced Bladder Cancer by Liquid Biopsy Analysis

Of the patients undergoing radical cystectomy, 20–80% experience relapse. Minimally invasive methods for early detection of metastatic relapse after cystectomy and for monitoring ongoing therapy are urgently needed to improve individualised follow-up and treatment. Therefore, we evaluated the use of circulating tumour DNA (ctDNA) in plasma and urine to detect metastatic relapse after cystectomy and measure treatment efficacy. We exome sequenced tumour and germline DNA from patients with muscle-invasive bladder cancer and monitored ctDNA in 370 liquid biopsies throughout the disease courses by 84 personalised digital droplet polymerase chain reaction assays targeting 61 genes. Patients were prospectively recruited between 2013 and 2017. Patients with metastatic relapse had significantly higher ctDNA levels compared with disease-free patients (p < 0.001). The median positive lead time between ctDNA detection in plasma and diagnosis of relapse was 101 d after cystectomy (range 0–932 d). Early detection of metastatic relapse and treatment response using liquid biopsies represents a novel, highly sensitive tool for monitoring patients, supporting clinicians, and guiding treatment decisions.

Remaining local subclinical joint inflammation is associated with deteriorated metacarpeal head bone microarchitecture in rheumatoid arthritis patients low disease activity

Objectives

Bone alterations at the subchondral level during rheumatoid arthritis (RA) remain under investigation. It remains unknown whether subchondral bone damage might still occur in RA patients in clinical remission, which could then infer suggesting that even minor subclinical inflammatory changes in the joint can induce local bone loss.

Long-term management of luminal urethral stricture in women

Introduction and hypothesis

The objective was to report our long-term experience of luminal urethral stricture (LUS) in women treated with dilation under general anesthesia.

Methods

Following institutional review board approval, charts of women who underwent urethral dilation (UD) under general anesthesia for LUS and had over 6 months’ follow-up were reviewed. LUS was confirmed by urethroscopy. UD was performed using female dilators with guidewire and Heyman dilators when required. Outcome measures included the number of UD procedures and the duration and frequency of clean intermittent catheterization (CIC). Success was defined as the ability to void without repeat UD and with no need for CIC 1 year after UD. Possible predictive variables were analyzed.

Results

Between 2000 and 2013, a total of 30 out of the 32 women who underwent UD for LUS met the inclusion criteria. Mean follow-up was 59 (range: 7 to 151) months. Thirteen women in the success group showed improvement in the mean maximum flow rate (pre 11 ml/s to post 27.8 ml/s) and post-void residual (pre 85 ml to post 43 ml). In the failure group of 17 patients, 2 required chronic CIC 1 year after a single UD. Fifteen opted for repeat UD. After second (n?=?5), third (n?=?2), and fourth (n?=?2) UD, 9 patients came off CIC and reported durable satisfaction. Four women remained on regular CIC. Two required a permanent suprapubic catheter.

Conclusion

At a mean follow-up of 5 years, UD for LUS produced durable resolution in 43 % of our patients. Another 30 % fully benefited from repeat UDs. Shorter duration of symptoms before presentation was significantly associated with success.