Florbetaben PET imaging to detect amyloid beta plaques in Alzheimer's disease: phase 3 study.

BACKGROUND: Evaluation of brain ß-amyloid by positron emission tomography (PET) imaging can assist in the diagnosis of Alzheimer disease (AD) and other dementias. METHODS: Open-label, nonrandomized, multicenter, phase 3 study to validate the (18)F-labeled ß-amyloid tracer florbetaben by comparing in vivo PET imaging with post-mortem histopathology. RESULTS: Brain images and tissue from 74 deceased subjects (of 216 trial participants) were analyzed. Forty-six of 47 neuritic ß-amyloid-positive cases were read as PET positive, and 24 of 27 neuritic ß-amyloid plaque-negative cases were read as PET negative (sensitivity 97.9% [95% confidence interval or CI 93.8-100%], specificity 88.9% [95% CI 77.0-100%]). In a subgroup, a regional tissue-scan matched analysis was performed. In areas known to strongly accumulate ß-amyloid plaques, sensitivity and specificity were 82% to 90%, and 86% to 95%, respectively. CONCLUSIONS: Florbetaben PET shows high sensitivity and specificity for the detection of histopathology-confirmed neuritic ß-amyloid plaques and may thus be a valuable adjunct to clinical diagnosis, particularly for the exclusion of AD. TRIAL REGISTRATION: ClinicalTrials.govNCT01020838.

Age dependence of brain ß-amyloid deposition in Down syndrome: An [18F]florbetaben PET study.

OBJECTIVE: To investigate brain ß-amyloid binding in subjects with Down syndrome (DS) using [(18)F]florbetaben PET imaging. METHODS: Thirty-nine subjects with DS (46.3 ± 4.7 years) were assessed with [(18)F]florbetaben PET imaging. Three blinded independent readers assessed the scans to provide a visual analysis. The primary quantitative imaging outcome was a standardized uptake value ratio (SUVR) obtained for 6 brain regions. Cognitive status was evaluated using the Dementia Screening Questionnaire for Individuals with Intellectual Disabilities (DSQIID). RESULTS: [(18)F]Florbetaben uptake was correlated with age (p < 0.0001, R(2) = 0.39); 90% of scans in subjects with DS aged 50 years or older (SUVR = 1.62 ± 0.26), 53% in those aged 45 to 49 years (SUVR = 1.43 ± 0.16), and 7% in those aged 40 to 45 years (SUVR = 1.27 ± 0.11) were visually assessed as positive. Visual and quantitative assessments were highly related (χ(2) = 11.3823, p = 0.0007; Cohen κ = 0.58). Only 2 of 34 participants were considered to have dementia by the DSQIID. CONCLUSIONS: Brain ß-amyloid binding, as measured by [(18)F]florbetaben, increases with age in DS. Subjects with DS who have no evidence of dementia demonstrate brain ß-amyloid binding in vivo, suggesting that [(18)F]florbetaben PET imaging may detect ß-amyloid in this at-risk population.

Aß imaging with 18F-florbetaben in prodromal Alzheimer's disease: a prospective outcome study.

BACKGROUND: We assessed the clinical utility of ß-amyloid (Aß) imaging with (18)F-florbetaben (FBB) in mild cognitive impairment (MCI) by evaluating its prognostic accuracy for progression to Alzheimer's disease (AD), comparing semiquantitative with visual scan assessment, and exploring the relationships among Aß, hippocampal volume (HV) and memory over time. METHODS: 45 MCI underwent FBB positron emission tomography, MRI and neuropsychological assessment at baseline and 2 years and clinical follow-up at 4 years. Positive FBB (FBB+), defined by a cortical to cerebellar cortex standardised uptake value ratio (SUVR) ≥ 1.45, was compared with visual assessment by five readers. Amnestic MCI (aMCI) was defined by a composite episodic memory (EM) Z-score of <-1.5. RESULTS: At baseline, 24 (53%) MCI were FBB+. Majority reads agreed with SUVR classification (κ 0.96). In 2 years, 18 (75%) FBB+ progressed to AD compared with 2 (9.5%) FBB-, yielding a predictive accuracy of 83% (95% CI 61% to 94%). Four FBB- developed non-AD dementia. Predictive accuracies of HV (58% (95% CI 42% to 73%)) and aMCI status (73% (95% CI 58% to 81%)) were lower. Combinations did not improve accuracy. By 4 years, 21 (87.5%) FBB+ had AD whereas 5 (24%) FBB- had non-AD dementia yielding a predictive accuracy of 94% (95% CI 74% to 99%). While the strong baseline association between FBB SUVR and EM declined over 2 years, the association between EM and HV became stronger. FBB SUVR increased 2.2%/year in FBB+ with no change in FBB-. CONCLUSIONS: (18)F-florbetaben Aß imaging facilitates accurate detection of prodromal AD. As neurodegeneration progresses, and in contrast with the early stages of the disease, hippocampal atrophy and not Aß, seems to drive memory decline. TRIAL REGISTRATION NUMBER: NCT01138111.

PET quantification of 18F-florbetaben binding to ß-amyloid deposits in human brains.

UNLABELLED: (18)F-florbetaben is a novel (18)F-labeled tracer for PET imaging of ß-amyloid deposits in the human brain. We evaluated the kinetic model-based approaches to the quantification of ß-amyloid binding in the brain from dynamic PET data. The validity of the practically useful tissue ratio was also evaluated against the model-based parameters. METHODS: (18)F-florbetaben PET imaging was performed with concurrent multiple arterial sampling after tracer injection (300 MBq) in 10 Alzheimer disease (AD) patients and 10 age-matched healthy controls. Regional brain-tissue time-activity curves for 90 min were analyzed by a 1-tissue-compartment model and a 2-tissue-compartment model (2TCM) with metabolite-corrected plasma data estimating the specific distribution volume (VS) and distribution volume ratio (DVR [2TCM]) and a multilinear reference tissue model estimating DVR (DVR [MRTM]) using the cerebellar cortex as the reference tissue. Target-to-reference tissue standardized uptake value ratios (SUVRs) at 70-90 min were also calculated. RESULTS: All brain regions required 2TCM to describe the time-activity curves. All ß-amyloid binding parameters in the cerebral cortex (VS, DVR [2TCM], DVR [MRTM], and SUVR) were significantly increased in AD patients (P < 0.05), and there were significant linear correlations among these parameters (r(2) > 0.83). Effect sizes in group discrimination between 8 ß-amyloid-positive AD scans and 9 ß-amyloid-negative healthy control scans for all binding parameters were excellent, being largest for DVR (2TCM) (4.22) and smallest for VS (3.25) and intermediate and the same for DVR (MRTM) and SUVR (4.03). CONCLUSION: These results suggest that compartment kinetic model-based quantification of ß-amyloid binding from (18)F-florbetaben PET data is feasible and that all ß-amyloid binding parameters including SUVR are excellent in discriminating between ß-amyloid-positive and -negative scans.

(18)F-florbetaben Aß imaging in mild cognitive impairment.

INTRODUCTION: (18)F-florbetaben and positron emission tomography were used to examine the relationships between ß-amyloid (Aß) deposition, cognition, hippocampal volume, and white matter hyperintensities in mild cognitive impairment (MCI). METHODS: Forty-five MCI participants were evaluated. A neocortical standardized uptake value ratio threshold ≥ 1.45 was used to discriminate high from low Aß burden. Correlations were adjusted for age, gender and years of education. RESULTS: High Aß burden was found in 53% of MCI. Regression analyses showed standardized uptake value ratio (r = -0.51, P = 0.0015) and hippocampal volume (r = 0.60, P = 0.024) both contributing to episodic memory impairment in independent fashion. White matter hyperintensities correlated with nonmemory cognition, and this correlation was particularly associated with Aß burden. CONCLUSION: Higher Aß deposition in MCI is associated with more severe memory impairment and is contributing to early amnestic symptoms independent of hippocampal atrophy.

Prediction of amyloid-ß pathology in amnestic mild cognitive impairment with neuropsychological tests.

Assessment of disease biomarkers, particularly the in vivo assessment of amyloid-ß (Aß) burden with positron emission tomography (PET), is gradually becoming central to the diagnosis of mild cognitive impairment (MCI) due to Alzheimer's disease (AD). However, the incorporation of biomarker evidence to the diagnostic process is currently restricted mainly to research settings. The identification of memory measures that are associated with Aß is of clinical relevance as this may enhance the confidence in making a diagnosis of MCI due to AD in clinical settings. Forty one persons with amnestic MCI underwent Aß imaging with (18)F-Florbetaben PET, magnetic resonance imaging, and a comprehensive neuropsychological assessment. All measures of episodic memory were significantly correlated with Aß burden, but regression analyses revealed a strong and selective association between story recall and Aß over and beyond the effects of age, education, global cognition, hippocampal volume, or other memory tests. Analyses of sensitivity and specificity of memory measures to detect high versus low Aß scans suggested that word-list recall performed better when high sensitivity was preferred, whereas story recall performed better when high specificity was preferred. In conclusion, a measure of story recall may increase the confidence in making a diagnosis of MCI due to AD in clinical settings.

Influence of scan duration on the accuracy of ß-amyloid PET with florbetaben in patients with Alzheimer's disease and healthy volunteers.

PURPOSE: Florbetaben is a ß-amyloid-targeted PET tracer with significant potential for augmenting the toolbox in the clinical diagnosis of Alzheimer's disease (AD). In dementia imaging, shortening of scan duration may simplify future clinical use. The aim of this retrospective study was to investigate the effect of scan duration on diagnostic accuracy. METHODS: PET scans obtained from 25 AD patients and 25 healthy volunteers (HVs) were analysed. In each subject, scans of three different durations (5, 10 and 20 min; all starting 90 min after injection) were obtained, randomized, and visually assessed by three experts blinded to the subject's identity and group affiliation. Presence/absence of ß-amyloid and diagnostic confidence (0-100 %) were scored, and 10 % of the scans were re-read. Further, randomly selected datasets of ten AD patients and ten HVs were quantified using an established VOI-based approach and using a voxel-based approach. RESULTS: The sensitivity and specificity of the blinded read were 80 % and 96 %, respectively, for all scan durations. Diagnostic confidence was high (97 ± 6 %, 97 ± 6 % and 95 ± 8 % for the 20-min, 10-min and 5-min scans, respectively; n.s.), as was interreader agreement (kappa(20 min) = 0.94, kappa(10 min) = 0.94, kappa(5 min) = 0.89; n.s.). Intrareader agreement was highest for the 20-min scan (kappa = 1.00) and lower for the 10-min scan (kappa = 0.71) and 5-min scan (kappa = 0.80; p = 0.002 and 0.003 vs. the 20-min scan). For all scan durations, composite SUVRs (Cohen's d effect size 4.5, 3.9 and 4.8 for the 5-min, 10-min and 20-min scans; p < 0.0001 each) and individual brain volumes affected by ß-amyloid (Cohen's d effect size 1.6, 1.8 and 2.0 for the 5-min, 10-min and 20-min scans; p < 0.005 each) were significantly higher in AD patients than in HVs. CONCLUSION: Reduction in scan duration did not relevantly affect the accuracy of florbetaben PET scans in discriminating between AD patients and HVs. Thus, a reduction in scan duration seems conceivable for the future clinical use of florbetaben.

Amyloid imaging with (18)F-florbetaben in Alzheimer disease and other dementias.

UNLABELLED: Amyloid imaging with (18)F-labeled radiotracers will allow widespread use, facilitating research, diagnosis, and therapeutic development for Alzheimer disease. The purpose of the study program was to compare cortical amyloid deposition using (18)F-florbetaben and PET in controls and subjects with mild cognitive impairment (MCI), frontotemporal lobar degeneration (FTLD), dementia with Lewy bodies (DLB), vascular dementia (VaD), Parkinson disease (PD), and Alzheimer disease (AD). METHODS: One hundred nine subjects in 3 clinical studies at Austin Health were reviewed: 32 controls, 20 subjects with MCI, and 30 patients with AD, 11 with FTLD, 7 with DLB, 5 with PD, and 4 with VaD underwent PET after intravenous injection of 300 MBq of (18)F-florbetaben. Standardized uptake value ratios (SUVR) using the cerebellar cortex as a reference region were calculated between 90 and 110 min after injection. RESULTS: When compared with the other groups, AD patients demonstrated significantly higher SUVRs (P < 0.0001) in neocortical areas. Most AD patients (96%) and 60% of MCI subjects showed diffuse cortical (18)F-florbetaben retention. In contrast, only 9% of FTLD, 25% of VaD, 29% of DLB, and no PD patients and 16% of controls showed cortical binding. Although there was a correlation between Mini Mental State Examination and ß-amyloid burden in the MCI group, no correlation was observed in controls, FTLD or AD. CONCLUSION: (18)F-florbetaben had high sensitivity for AD, clearly distinguished patients with FTLD from AD, and provided results comparable to those reported with (11)C-Pittsburgh Compound B in a variety of neurodegenerative diseases.

Individualized quantification of brain ß-amyloid burden: results of a proof of mechanism phase 0 florbetaben PET trial in patients with Alzheimer's disease and healthy controls.

PURPOSE: Complementing clinical findings with those generated by biomarkers--such as ß-amyloid-targeted positron emission tomography (PET) imaging--has been proposed as a means of increasing overall accuracy in the diagnosis of Alzheimer's disease (AD). Florbetaben ([(18)F]BAY 94-9172) is a novel ß-amyloid PET tracer currently in global clinical development. We present the results of a proof of mechanism study in which the diagnostic efficacy, pharmacokinetics, safety and tolerability of florbetaben were assessed. The value of various quantitative parameters derived from the PET scans as potential surrogate markers of cognitive decline was also investigated. METHODS: Ten patients with mild-moderate probable AD (DSM-IV and NINCDS-ADRDA criteria) and ten age-matched (≥ 55 years) healthy controls (HCs) were administered a single dose of 300 MBq florbetaben, which contained a tracer mass dose of < 5 µg. The 70-90 min post-injection brain PET data were visually analysed by three blinded experts. Quantitative assessment was also performed via MRI-based, anatomical sampling of predefined volumes of interest (VOI) and subsequent calculation of standardized uptake value (SUV) ratios (SUVRs, cerebellar cortex as reference region). Furthermore, single-case, voxelwise analysis was used to calculate individual "whole brain ß-amyloid load". RESULTS: Visual analysis of the PET data revealed nine of the ten AD, but only one of the ten HC brains to be ß-amyloid positive (p = 0.001), with high inter-reader agreement (weighted kappa ≥ 0.88). When compared to HCs, the neocortical SUVRs were significantly higher in the ADs (with descending order of effect size) in frontal cortex, lateral temporal cortex, occipital cortex, anterior and posterior cingulate cortices, and parietal cortex (p = 0.003-0.010). Voxel-based group comparison confirmed these differences. Amongst the PET-derived parameters, the Statistical Parametric Mapping-based whole brain ß-amyloid load yielded the closest correlation with the Mini-Mental State Examination scores (r = -0.736, p < 0.001), following a nonlinear regression curve. No serious adverse events or other safety concerns were seen. CONCLUSION: These results indicate florbetaben to be a safe and efficacious ß-amyloid-targeted tracer with favourable brain kinetics. Subjects with AD could be easily differentiated from HCs by both visual and quantitative assessment of the PET data. The operator-independent, voxel-based analysis yielded whole brain ß-amyloid load which appeared valuable as a surrogate marker of disease severity.

Cerebral amyloid-ß PET with florbetaben (18F) in patients with Alzheimer's disease and healthy controls: a multicentre phase 2 diagnostic study.

BACKGROUND: Imaging with amyloid-ß PET can potentially aid the early and accurate diagnosis of Alzheimer's disease. Florbetaben (¹8F) is a promising ¹8F-labelled amyloid-ß-targeted PET tracer in clinical development. We aimed to assess the sensitivity and specificity of florbetaben (¹8F) PET in discriminating between patients with probable Alzheimer's disease and elderly healthy controls. METHODS: We did a multicentre, open-label, non-randomised phase 2 study in 18 centres in Australia, Germany, Switzerland, and the USA. Imaging with florbetaben (¹8F) PET was done on patients with probable Alzheimer's disease (age 55 years or older, mini-mental state examination [MMSE] score=18-26, clinical dementia rating [CDR]=0·5-2·0) and age-matched healthy controls (MMSE ≥ 28, CDR=0). Our primary objective was to establish the diagnostic efficacy of the scans in differentiating between patients with probable disease and age-matched healthy controls on the basis of neocortical tracer uptake pattern 90-110 min post-injection. PET images were assessed visually by three readers masked to the clinical diagnosis and all other clinical findings, and quantitatively by use of pre-established brain volumes of interest to obtain standard uptake value ratios (SUVRs), taking the cerebellar cortex as the reference region. This study is registered with ClinicalTrials.gov, number NCT00750282. FINDINGS: 81 participants with probable Alzheimer's disease and 69 healthy controls were assessed. Independent visual assessment of the PET scans showed a sensitivity of 80% (95% CI 71-89) and a specificity of 91% (84-98) for discriminating participants with Alzheimer's disease from healthy controls. The SUVRs in all neocortical grey-matter regions in participants with Alzheimer's disease were significantly higher (p < 0·0001) compared with the healthy controls, with the posterior cingulate being the best discriminator. Linear discriminant analysis of regional SUVRs yielded a sensitivity of 85% and a specificity of 91%. Regional SUVRs also correlated well with scores of cognitive impairment such as the MMSE and the word-list memory and word-list recall scores (r -0·27 to -0·33, p ≤ 0·021). APOE ɛ4 was more common in participants with positive PET images compared with those with negative scans (65%vs 22% [p=0·027] in patients with Alzheimer's disease; 50%vs 16% [p = 0·074] in healthy controls). No safety concerns were noted. INTERPRETATION: We provide verification of the efficacy, safety, and biological relevance of florbetaben (¹8F) amyloid-ß PET and suggest its potential as a visual adjunct in the diagnostic algorithm of dementia. FUNDING: Bayer Schering Pharma AG.

Parkinson's disease is overdiagnosed clinically at baseline in diagnostically uncertain cases: a 3-year European multicenter study with repeat [123I]FP-CIT SPECT.

Overdiagnosis of Parkinson's disease (PD) is suggested by specialist review of community diagnosis, and in postmortem studies. In specialist centers 4 to 15% of patients entered into clinical trials as early PD do not have functional imaging support for a PD diagnosis. In a European multicenter, prospective, longitudinal study, we compared clinical diagnosis with functional SPECT imaging using [123I]FP-CIT (DaTSCAN, GE Healthcare). Repeat observations were performed over 3 years in patients with tremor and/or parkinsonism in whom there was initial diagnostic uncertainty between degenerative parkinsonism and nondegenerative tremor disorders. Video-recording of clinical features was scored independently of functional imaging results by two blinded clinicians at 36 months (= gold standard clinical diagnosis). Three readers, unaware of the clinical diagnosis, classified the images as normal or abnormal by visual inspection. The main endpoint was the sensitivity and specificity of SPECT imaging at baseline compared with the gold standard. In 99 patients completing the three serial assessments, on-site clinical diagnosis overdiagnosed degenerative parkinsonism at baseline in diagnostically uncertain cases compared with the gold standard clinical diagnosis (at 36 months), the latter giving a sensitivity of 93% and specificity of 46%. The corresponding baseline [123I]FP-CIT SPECT results showed a mean sensitivity of 78% and a specificity of 97%. Inter-reader agreement for rating scans as normal or abnormal was high (Cohen's kappa = 0.94-0.97).

Diagnostic accuracy of 123I-FP-CIT SPECT in possible dementia with Lewy bodies.

BACKGROUND: (123)I-FP-CIT SPECT (single photon emission computed tomography) can help in the differential diagnosis of probable dementia with Lewy bodies (Lewy body dementia) and Alzheimer's disease. AIMS: Our aim was to determine the accuracy of (123)I-FP-CIT SPECT in diagnosing people with possible dementia with Lewy bodies. METHOD: We undertook a 12-month follow-up of 325 individuals with probable or possible Lewy body or non-Lewy body dementia who had previously undergone (123)I-FP-CIT SPECT. A consensus panel, masked to SPECT findings, established diagnosis at 12 months in 264 people. RESULTS: Of 44 people with possible dementia with Lewy bodies at baseline, at follow-up the diagnosis for 19 people was probable dementia with Lewy bodies (43%), in 7 people non-Lewy body dementia (16%) and for 18 individuals it remained possible dementia with Lewy bodies (41%). Of the 19 who at follow-up were diagnosed with probable dementia with Lewy bodies, 12 had abnormal scans at baseline (sensitivity 63%); all 7 individuals with a possible diagnosis who were diagnosed as having Alzheimer's disease at follow-up had normal scans (specificity 100%). CONCLUSIONS: Our findings confirm the diagnostic accuracy of (123)I-FP-CIT SPECT in distinguishing Lewy body from non-Lewy body dementia and also suggest a clinically useful role in diagnostically uncertain cases, as an abnormal scan in a person with possible dementia with Lewy bodies is strongly suggestive of dementia with Lewy bodies.

Sensitivity and specificity of dopamine transporter imaging with 123I-FP-CIT SPECT in dementia with Lewy bodies: a phase III, multicentre study.

BACKGROUND: Dementia with Lewy bodies (DLB) needs to be distinguished from other types of dementia because of important differences in patient management and outcome. Current clinically based diagnostic criteria for DLB have limited accuracy. Severe nigrostriatal dopaminergic degeneration occurs in DLB, but not in Alzheimer's disease or most other dementia subtypes, offering a potential system for a biological diagnostic marker. The primary aim of this study was to investigate the sensitivity and specificity, in the ante-mortem differentiation of probable DLB from other causes of dementia, of single photon emission computed tomography (SPECT) brain imaging with the ligand (123)I-2beta-carbometoxy-3beta-(4-iodophenyl)-N-(3-fluoropropyl) nortropane ((123)I-FP-CIT), which binds to the dopamine transporter (DAT) reuptake site. Diagnostic accuracy, positive and negative predictive values, and inter-reader agreement were the secondary endpoints and a subgroup of possible DLB patients was also included. METHODS: We did a phase III study in which we used a (123)I-FP-CIT SPECT scan to assess 326 patients with clinical diagnoses of probable (n=94) or possible (n=57) DLB or non-DLB dementia (n=147) established by a consensus panel (in 28 patients no diagnosis could be made). Three readers, unaware of the clinical diagnosis, classified the images as normal or abnormal by visual inspection. The study had 90% power to detect the differences between our anticipated sensitivity (0.80) and specificity (0.85) targets and prespecified lower thresholds (sensitivity 0.65, specificity 0.73) using one-sided binomial tests with a significance level of alpha=0.025. FINDINGS: Abnormal scans had a mean sensitivity of 77.7% for detecting clinical probable DLB, with specificity of 90.4% for excluding non-DLB dementia, which was predominantly due to Alzheimer's disease. A mean value of 85.7% was achieved for overall diagnostic accuracy, 82.4% for positive predictive value, and 87.5% for negative predictive value. Inter-reader agreement for rating scans as normal or abnormal was high (Cohen's kappa=0.87). The procedure was well tolerated with few adverse events. INTERPRETATION: A revision of the International Consensus Criteria for DLB has recommended that low DAT uptake in the basal ganglia, as shown by SPECT or PET imaging, be a suggestive feature for diagnosis. Our findings confirm the high correlation between abnormal (low binding) DAT activity measured with (123)I-FP-CIT SPECT and a clinical diagnosis of probable DLB. The diagnostic accuracy is sufficiently high for this technique to be clinically useful in distinguishing DLB from Alzheimer's disease.

Renal artery stenosis: functional assessment with dynamic MR perfusion measurements--feasibility study.

PURPOSE: To prospectively assess feasibility of renal magnetic resonance (MR) perfusion measurement method based on turbo fast low-angle shot sequences for grading effect of renal artery stenosis (RAS) on parenchymal perfusion. MATERIALS AND METHODS: Institutional review board approved this study, and patients gave written consent. Seventy-three patients (34 male, 39 female; age range, 17-84 years) who were clinically suspected of having RAS underwent contrast material-enhanced (gadodiamide) saturation-recovery turbo fast low-angle shot imaging for measurement of renal perfusion and high-spatial-resolution MR angiography for RAS detection and grading. Degree of stenosis was evaluated as high grade (>/=75% stenosis), low to intermediate grade (>0% to <75% stenosis), or absent. High temporal resolution of the turbo fast low-angle shot sequence allowed acquisition of an exact first-pass tracing of the contrast agent bolus from which a signal intensity (SI)-time curve was derived. On the basis of this curve, mean transit time (MTT) of the contrast agent bolus, maximal upslope (MUS) of the curve, maximum SI, and time to SI peak (TTP) were calculated with a gamma variate fit. Wilcoxon rank sum test, Pearson product moment correlation, and paired t test were used for statistical analysis. RESULTS: Twenty-four renal arteries had high-grade RAS, 12 renal arteries had low- to intermediate-grade RAS, and 104 renal arteries had no RAS. Significant differences between patients without stenoses or with low- to intermediate-grade stenoses and patients with high-grade stenoses were found for MTT, MUS, and TTP (P < .001). Perfusion parameters were correlated with patients' serum creatinine levels, and significant correlations were found for MTT (r = 0.41), MUS (r = 0.48), and TTP (r = 0.4), with P < .001. CONCLUSION: MR perfusion parameters can be used to assess effect of RAS on parenchymal perfusion. Perfusion measurements reflect renal function as measured with serum creatinine levels.

Endovascular repair of inflammatory abdominal aortic aneurysms: a valuable alternative?--Case report and review of literature.

While endovascular repair (ER) has become a routine procedure in the treatment of arteriosclerotic abdominal aortic aneurysms with a suitable configuration, only rare reports of interventional treatment of inflammatory aortic abdominal aneurysms (IAAA) exist. We present a case study of a male patient with IAAA, who presented with inflammatory thickening involving the entire circumference of the aortic vessel wall. The MRI performed 8 months after successful ER demonstrated complete regression of vessel wall induration. A patient with the appropriate anatomical configuration of IAAA should benefit from the lower morbidity and mortality of endovascular aneurysm repair (EVAR). In our view, EVAR is preferable to open surgical repair in the specific situation of IAAA.

Evidence of luminal phosphatidylcholine secretion in rat ileum.

BACKGROUND: Intestinal mucus not only facilitates substrate absorption, but also forms a hydrophobic, phosphatidylcholine (PC) enriched, barrier against luminal gut contents. METHODS: For evaluation of the origin of PC in intestinal mucus, we first analyzed the mucus PC in mice with absent biliary phospholipid secretion (mdr2 (-/-) mice) using electrospray ionization (ESI) tandem mass spectroscopy (MS/MS). Second, in situ perfused rat jejunum, ileum and colon were analyzed after i.v. bolus injections of 155 pmol [(3)H]-PC. Additional in vitro experiments were performed with isolated mucosal cells after incubation with the PC precursor [(3)H]-choline. RESULTS: In mdr2 (-/-) mice and control animals no significant quantitative difference in mucus PC was found, indicating that mucus PC is of intestinal and not biliary origin. In situ perfusion studies detected intestinal secretion of [(3)H]-PC, which was stimulated in presence of 2 mM taurocholate (TC). Secretion rates of [(3)H]-PC were highest in ileum (9.0+/-0.8 fmol h(-1)xcm(-1)), lower in jejunum (4.3+/-0.5) and minimal in colon (0.8+/-0.2). It compares to an intestinal secretion of native PC originating to 64% from bile, 9% from jejunum, 28% from ileum, and 1% from colon. Complementary in vitro studies showed 30-min secretion rates for [(3)H]-PC to be highest in enterocytes from ileum (26.5+/-5.3% of intracellular [(3)H]-PC) and jejunum (19.8+/-2.9%), and significantly lower in colonocytes (8.4+/-1.3%). CONCLUSION: PC in the intestinal mucus originates from secretion by ileal and jejunal enterocytes.