Immunologic and Genetic Contributors to CD46-Dependent Immune Dysregulation.

Mutations in CD46 predispose to atypical hemolytic uremic syndrome (aHUS) with low penetrance. Factors driving immune-dysregulatory disease in individual mutation carriers have remained ill-understood. In addition to its role as a negative regulator of the complement system, CD46 modifies T cell-intrinsic metabolic adaptation and cytokine production. Comparative immunologic analysis of diseased vs. healthy CD46 mutation carriers has not been performed in detail yet. In this study, we comprehensively analyzed clinical, molecular, immune-phenotypic, cytokine secretion, immune-metabolic, and genetic profiles in healthy vs. diseased individuals carrying a rare, heterozygous CD46 mutation identified within a large single family. Five out of six studied individuals carried a CD46 gene splice-site mutation causing an in-frame deletion of 21 base pairs. One child suffered from aHUS and his paternal uncle manifested with adult-onset systemic lupus erythematosus (SLE). Three mutation carriers had no clinical evidence of CD46-related disease to date. CD4+ T cell-intrinsic CD46 expression was uniformly 50%-reduced but was comparable in diseased vs. healthy mutation carriers. Reconstitution experiments defined the 21-base pair-deleted CD46 variant as intracellularly-but not surface-expressed and haploinsufficient. Both healthy and diseased mutation carriers displayed reduced CD46-dependent T cell mitochondrial adaptation. Diseased mutation carriers had lower peripheral regulatory T cell (Treg) frequencies and carried potentially epistatic, private rare variants in other inborn errors of immunity (IEI)-associated proinflammatory genes, not found in healthy mutation carriers. In conclusion, low Treg and rare non-CD46 immune-gene variants may contribute to clinically manifest CD46 haploinsufficiency-associated immune-dysregulation.

The provisional OMERACT ultrasonography score for giant cell arteritis.

OBJECTIVES: To develop an Outcome Measures in Rheumatology (OMERACT) ultrasonography score for monitoring disease activity in giant cell arteritis (GCA) and evaluate its metric properties. METHODS: The OMERACT Instrument Selection Algorithm was followed. Forty-nine members of the OMERACT ultrasonography large vessel vasculitis working group were invited to seven Delphi rounds. An online reliability exercise was conducted using images of bilateral common temporal arteries, parietal and frontal branches as well as axillary arteries from 16 patients with GCA and 7 controls. Sensitivity to change and convergent construct validity were tested using data from a prospective cohort of patients with new GCA in which ultrasound-based intima-media thickness (IMT) measurements were conducted at weeks 1, 3, 6, 12 and 24. RESULTS: Agreement was obtained (92.7%) for the OMERACT GCA Ultrasonography Score (OGUS), calculated as follows: sum of IMT measured in every segment divided by the rounded cut-off values of IMTs in each segment. The resulting value is then divided by the number of segments available. Thirty-five members conducted the reliability exercise, the interrater intraclass correlation coefficient (ICC) for the OGUS was 0.72-0.84 and the median intrareader ICC was 0.91. The prospective cohort consisted of 52 patients. Sensitivity to change between baseline and each follow-up visit up to week 24 yielded standardised mean differences from -1.19 to -2.16, corresponding to large and very large magnitudes of change, respectively. OGUS correlated moderately with erythrocyte sedimentation rate, C reactive protein and Birmingham Vasculitis Activity Score (corrcoeff 0.37-0.48). CONCLUSION: We developed a provisional OGUS for potential use in clinical trials.

Prior polymyalgia rheumatica is associated with sonographic vasculitic changes in newly diagnosed patients with giant cell arteritis.

OBJECTIVES: To investigate the hypothesis that a history of polymyalgia rheumatica (PMR) is associated with a more severe and damaging disease course in newly diagnosed giant cell arteritis (GCA) patients. METHODS: Retrospective analysis of GCA patients diagnosed between 12/2006 and 05/2021. We compared vascular ultrasound findings (presence of vasculitis and vascular stenosis) in GCA patients with and without prior PMR. RESULTS: 49 of 311 GCA patients (15.8%) had prior PMR in median 30.6 (IQR 7.1-67.3) months before GCA diagnosis. Patients with prior PMR had more often large vessel vasculitis (LVV) (51.0% vs 25.0%, p< 0.001) and stenosis within the vasculitic segments (18.4% vs 3.1%, p< 0.001) on ultrasound. In multivariable analysis, prior PMR remained significantly associated with LVV (OR 7.65, 95% CI 2.72-23.97, p< 0.001). Polymyalgic symptoms at GCA diagnosis in the patients without prior PMR were not associated with a higher prevalence of LVV (p= 0.156). CONCLUSION: Patients with a diagnosis of PMR before GCA diagnosis had two times more often large vessel involvement and significant more vasculitic stenoses on ultrasound examination than patients without prior PMR. Pre-existing PMR is an independent risk factor for more extensive and advanced ultrasound findings at GCA diagnosis. The contribution of subclinical vasculitis to disease associated damage has to be further studied.

Practical guide of vascular ultrasound in arteriovenous fistulae.

The use of vascular ultrasound, especially with the increasing prevalence of percutaneous arteriovenous fistulas, has taken a central role as a diagnostic and therapeutic imaging procedure in vascular access creation. The current review article stresses the importance of vascular ultrasound in arteriovenous fistula, from planning to creation to maintenance. It summarises and gives practical guidance regarding sonographic criteria for vascular access procedure planning, the application of vascular ultrasound intraoperatively and during follow-up. Ultrasound education and training modalities to meet high standards of patient care in hemodialysis are presented.

[18F]FDG positron emission tomography and ultrasound in the diagnosis of giant cell arteritis: congruent or complementary imaging methods?

OBJECTIVES: [18F]Fluorodeoxyglucose (FDG)-PET/CT and US are both well established for diagnosing GCA. The present study investigates their accuracy and whether they provide overlapping or complementary information in a cohort of patients presenting with suspicion of GCA. METHODS: We selected consecutive patients from our cohort of suspected GCA cases that underwent both extended vascular US and PET/CT for diagnostic work-up between December 2006 and August 2012. RESULTS: A total of 102 patients were included. Diagnosis of GCA was confirmed in 68 patients and excluded in 34 patients (controls). Vasculitic changes in US were most often found in the temporal artery with 32 positive findings on each side, followed by the popliteal artery (10 right, 9 left) and the subclavian/axillary artery (7 right, 8 left). By contrast, PET/CT showed vasculitis most frequently in the vertebral (23 right, 33 left) and common carotid arteries (32 right, 24 left), followed by the subclavian arteries (16 right, 18 left), and the thoracic (17) and abdominal aorta (23). In 37/68 GCA patients PET/CT and US both revealed vasculitic findings, 11/68 had positive findings in US only and 14/68 in PET/CT only. Specificity of US was higher (one false-positive vs five false-positive in PET/CT). On a single segment level, only 20 of 136 positive segments were positive in both imaging modalities. CONCLUSION: PET/CT measuring vessel wall metabolism and US vessel wall morphology showed a comparable diagnostic accuracy for GCA. However PET/CT and US were often discrepant within single vascular regions. Thus PET/CT and US should be considered as complementary methods, with a second imaging modality increasing the diagnostic yield by 16-20%.

Bedside hand vein inspection for noninvasive central venous pressure assessment.

Rapid estimates of the central venous pressure (CVP) can be helpful to administer early fluid therapy or to manage cardiac preload in intensive care units, operating rooms or emergency rooms in order to start and monitor an adequate medical therapy. Invasive CVP measurements have inherent and non-negligible complication rates as well as great expenditures. Several noninvasive methods of CVP measurements, like ultrasound-guided techniques, are available, but require trained skills and special equipment which might not be at hand in all situations. Our purpose was to evaluate the feasibility and accuracy of CVP estimates assessed upon the height of hand veins collapse (HVC) using invasively measured CVP as the gold standard. The HVC was determined by slowly lifting the patient's hand while watching the dorsal hand veins to collapse. The vertical distance from the dorsal hand to a transducer air zero port was noted and converted to mmHg. The observer was blinded to the simultaneously measured CVP values, which were categorized as low (<7 mmHg), normal (7-12 mmHg) and high (>12 mmHg). Measurements were performed in 82 patients who had a median [IQR] age of 67 [60;74]. Median CVP was 12 [8;15] mmHg and the median absolute difference between the measured HVC and CVP was 4 [2;7] mmHg. The Spearman correlation coefficient between CVP and HVC was 0.55, 95%-CI [0.35;0.69]. Overall CVP categorization was correct in 45% of the cases. HVC had a sensitivity of 92% for a low CVP with a negative predictive value of 98%. A high HVC had a sensitivity of 29% but a high specificity of 94% for a high CVP. The overall performance of observing the hand vein collapse to estimate CVP was only moderate in the intensive care setting. However, the median difference to the CVP was low and HVC identifies a low CVP with a high sensitivity and excellent negative predictive value.

Vessel wall plasticity in large vessel giant cell arteritis: an ultrasound follow-up study.

OBJECTIVES: To assess changes of arterial vessel wall morphology in large vessel GCA patients (LV-GCA) by repeated US. METHODS: Patients with LV-GCA on US examination were followed up 6, 12 and 24 months after diagnosis by US of the temporal, vertebral, carotid (common, internal, external), subclavian, axillary, femoral (deep, superficial and common) and popliteal arteries. Clinical and laboratory data were assessed at each visit. Vessel wall thickening was classified as moderate, marked or arteriosclerotic. RESULTS: A total of 42 patients (26 female) with a median age of 75 years at diagnosis had in median 2 (range 1-3) US follow-up exams. Twenty-eight had both LV and temporal artery involvement and 14 had LV-GCA only. The common carotid, subclavian, axillary, popliteal and/or superficial femoral artery were most commonly involved. Reduction of LV wall thickening occurred in 45% of patients during follow-up, corresponding to 71 of the 284 (25%) initially 'vasculitic' LV segments. In contrast, a reduction of vessel wall thickening in the temporal artery was found in 85% of patients. Of the LVs, the vertebral, axillary, subclavian and deep femoral arteries were most likely to improve. There was no difference in relapses or the received cumulative steroid dose between patients with or without a reduction of vessel wall thickening (temporal artery or LV) during follow-up. CONCLUSION: Regression of wall thickening within the LV is significantly less common than in the temporal artery and irrespective of clinical remission. Morphological regression does not seem to be a useful predictor for relapses.

Risk stratification of elderly patients with acute pulmonary embolism.

BACKGROUND: Combining high-sensitivity cardiac Troponin T (hs-cTnT), NT-pro-B-type natriuretic peptide (NT-proBNP) and high-sensitivity C-reactive protein (hs-CRP) may improve risk stratification of patients with pulmonary embolism (PE) beyond the PESI risk score. METHODS: In the prospective multicentre SWITCO65+ study, we analysed 214 patients ≥ 65 years with a new submassive PE. Biomarkers and clinical information for the PESI risk score were ascertained within 1 day after diagnosis. Associations of hs-TnT, NT-proBNP, hs-CRP and the PESI risk score with the primary endpoint defined as 6-month mortality were assessed. The discriminative power of the PESI risk score and its combination with hs-cTnT, NT-proBNP and hs-CRP for 6-month mortality was compared using integrated discrimination improvement (IDI) index and net reclassification improvement (NRI). RESULTS: Compared with the lowest quartile, patients in the highest quartile had a higher risk of death during the first 6 months for hs-cTnT (adjusted HR 10.22; 95% CI 1.79-58.34; P = 0.009) and a trend for NT-proBNP (adjusted HR 4.3; 95% CI 0.9-20.41; P = 0.067) unlike hs-CRP (adjusted HR 1.97; 95% CI 0.48-8.05; P = 0.344). The PESI risk score (c-statistic 0.77 (95% CI 0.69-0.84) had the highest prognostic accuracy for 6-month mortality, outperforming hs-cTnT, NT-proBNP and hs-CRP (c-statistics of 0.72, 0.72, and 0.54), respectively. Combining all three biomarkers had no clinically relevant impact on risk stratification when added to the PESI risk score (IDI = 0.067; 95% CI 0.012-0.123; P = 0.018; NRI = 0.101 95% CI -0.099-0.302; P = 0.321). CONCLUSIONS: In elderly patients with PE, 6-month mortality can adequately be predicted by the PESI risk score alone.

Characteristics of autoantibodies targeting 14-3-3 proteins and their association with clinical features in newly diagnosed giant cell arteritis.

Objectives: Autoantibodies are useful biomarkers for diagnosing and monitoring treatment in some autoimmune diseases. Antibodies against isoforms of 14-3-3 protein have been proposed as biomarkers for the presence of aortic aneurysm in large-vessel vasculitis (LVV). Here, we aimed to evaluate the diagnostic role and potential immunopathological involvement of anti-14-3-3 antibodies in newly diagnosed LVV patients. Methods: Antibodies against three isoforms of 14-3-3 (γ, ɛ and ζ) were measured in 90 subjects: 48 GCA and 3 Takayasu's arteritis (TA) patients, and 39 controls (non-inflammatory and inflammatory diseases), using a multiplexed bead-based immunoassay and immunoprecipitation studies. The positive cut-off value was defined based on young healthy controls. Anti-14-3-3 IgG antibodies in LVV patients were compared with those in controls in order to assess their diagnostic performance, and the relationship of anti-14-3-3 IgG antibodies to the immunohistopathology of artery explants was assessed. Results: Antibodies against all three 14-3-3 isoforms were detected in LVV patients as well as in age-matched inflammatory and non-inflammatory controls. Among LVV patients, detection of antibodies targeting 14-3-3 ɛ and ζ was associated with more severe disease. Detection of antibodies against 14-3-3 γ was linked to latent Toxoplasma gondii infection, a parasite that secrets a 14-3-3 homologue, suggesting potential cross-reactivity. Conclusion: Detection of antibodies against 14-3-3 proteins at the time of LVV diagnosis is not disease-specific. Their presence at high levels in LVV patients with stroke, aortitis and-in a previous study-aneurysm formation may indicate an association with extensive tissue destruction. The relevance of 14-3-3 antibodies in non-LVV patients needs to be investigated in larger cohorts.

[Endoluminal Treatment of Varicose Veins: Value of Duplex Ultrasound (Part 2)]. / Endoluminale Varikosebehandlung: Stellenwert der Duplexsonografie (Teil 2).

Part one addressed the value of duplex ultrasound in the diagnostic workup of varicosis. The present article discusses the use of preinterventional, intrainterventional and postinterventional duplex ultrasound in endoluminal methods for the treatment of varices. It is a prerequisite for the planning, implementation, and follow-up of this form of therapy.

Non-enhanced, ECG-gated MR angiography of the pedal vasculature: comparison with contrast-enhanced MR angiography and digital subtraction angiography in peripheral arterial occlusive disease.

OBJECTIVES: This study was conducted in order to compare a high resolution, non-contrast-enhanced MRA (NATIVE SPACE, NE-MRA) of the pedal vasculature with contrast-enhanced MRA (CE-MRA) and digital subtraction angiography (DSA) in patients with peripheral arterial occlusive disease (PAOD). METHODS: The prospective study consists of 20 PAOD patients. All patients underwent percutaneous transluminal angioplasty or stenting and received MR angiographies the following day. RESULTS: With CE-MRA, 75.7 % of vessel segments showed good, 16.4 % suboptimal and 7.9 % not usable image quality. With NE-MRA, 64.6 % showed good, 18.6 % suboptimal and 16.8 % not usable image quality. CE-MRA showed a sensitivity and negative predictive value of 90 %/95 % regarding significant stenosis (greater than 50 %), and specificity and positive predictive value were 88 %/77 %. Accordingly, sensitivity and negative predictive value for the NE-MRA were 96 %/97 % and specificity and positive predictive value were 80 %/69 % for stenoses greater than 50 %. CONCLUSIONS: The applied NE-MRA technique achieves high diagnostic accuracy even in very small distal arteries of the foot. However, the rate of non-diagnostic vessel segments is considerably higher for NE-MRA than for CE-MRA. NE-MRA is a valuable alternative to CE-MRA in selected patients. KEY POINTS: • Comparison of non-enhanced MRA with contrast-enhanced MRA and DSA as gold standard. • High resolution MRA at 3 T for the depiction of small pedal vessels. • Evaluation of high resolution non-enhanced MRA in PAOD patients.

Polypharmacy is associated with an increased risk of bleeding in elderly patients with venous thromboembolism.

BACKGROUND: Polypharmacy, defined as the concomitant use of multiple medications, is very common in the elderly and may trigger drug-drug interactions and increase the risk of falls in patients receiving vitamin K antagonists. OBJECTIVE: To examine whether polypharmacy increases the risk of bleeding in elderly patients who receive vitamin K antagonists for acute venous thromboembolism (VTE). DESIGN: We used a prospective cohort study. PARTICIPANTS: In a multicenter Swiss cohort, we studied 830 patients aged ≥ 65 years with VTE. MAIN MEASURES: We defined polypharmacy as the prescription of more than four different drugs. We assessed the association between polypharmacy and the time to a first major and clinically relevant non-major bleeding, accounting for the competing risk of death. We adjusted for known bleeding risk factors (age, gender, pulmonary embolism, active cancer, arterial hypertension, cardiac disease, cerebrovascular disease, chronic liver and renal disease, diabetes mellitus, history of major bleeding, recent surgery, anemia, thrombocytopenia) and periods of vitamin K antagonist treatment as a time-varying covariate. KEY RESULTS: Overall, 413 (49.8 %) patients had polypharmacy. The mean follow-up duration was 17.8 months. Patients with polypharmacy had a significantly higher incidence of major (9.0 vs. 4.1 events/100 patient-years; incidence rate ratio [IRR] 2.18, 95 % confidence interval [CI] 1.32-3.68) and clinically relevant non-major bleeding (14.8 vs. 8.0 events/100 patient-years; IRR 1.85, 95 % CI 1.27-2.71) than patients without polypharmacy. After adjustment, polypharmacy was significantly associated with major (sub-hazard ratio [SHR] 1.83, 95 % CI 1.03-3.25) and clinically relevant non-major bleeding (SHR 1.60, 95 % CI 1.06-2.42). CONCLUSIONS: Polypharmacy is associated with an increased risk of both major and clinically relevant non-major bleeding in elderly patients receiving vitamin K antagonists for VTE.

Correlation of skeletal muscle blood oxygenation level-dependent MRI and skin laser Doppler flowmetry in patients with systemic sclerosis.

PURPOSE: To investigate the origin of skeletal muscle BOLD MRI alterations in patients with systemic sclerosis (SSc) by correlating BOLD MRI T2* signal of calf muscles with microcirculatory blood flow of calf skin measured by laser Doppler flowmetry (LDF). MATERIALS AND METHODS: BOLD MRI (3T) and LDF measurements were performed in 12 consecutive SSc patients (6 women, 6 men; mean age 54.0 ± 10.0 years) and 12 healthy volunteers (4 men, 8 women; mean age 44.7 ± 13.1 years). For both modalities, the same cuff compression paradigm at mid-thigh level was used. LDF datasets were acquired using a PeriScan PIM II Imager (Perimed AB, Stockholm, Sweden) at the upper calf corresponding to the level of MR imaging. Cross-correlations of BOLD and LDF signal intensity changes depending on time lags between both time series were calculated. RESULTS: Maximal cross-correlations of BOLD T2* and LDF measurements were calculated as 0.93 (healthy volunteers) and 0.94 (SSc patients) for a BOLD time lag of approximately 10 s. Key parameter analysis suggested that in contrast to hyperemic BOLD signal loss at maximum value in SSc patients, ischemic T2* decrease cannot be explained by differences of tissue perfusion. CONCLUSION: Skeletal muscle BOLD T2* signal in SSc patients is closely correlated with changes of microperfusion as detected by LDF.

Imaging to predict early relapses after treatment discontinuation in patients with large vessel giant cell arteritis - A cohort study.

OBJECTIVES: To investigate the value of [18F]fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) and magnetic resonance imaging (MRI) in predicting relapse after treatment discontinuation in patients with large-vessel giant cell arteritis (LV-GCA). METHODS: This study included patients with LV-GCA whose treatment was discontinued between 2018 and 2023. All patients underwent PET/CT and/or MRI at the time of treatment discontinuation in clinical remission. Qualitative and quantitative PET/CT scores, by measuring standardized uptake values (SUV), and semiquantitative MRI scores of the aorta and supraaortic vessels were compared between patients who relapsed within 4 months after treatment discontinuation and those who did not. RESULTS: Forty patients were included (median age 67.4 years, interquartile range (IQR) 60.8-74.0; 77.5 % females). Eleven patients (27.5 %) relapsed after treatment discontinuation (time to relapse 1.9 months, IQR 1.4-3.3). Patients who relapsed were comparable to those who remained in remission with respect to the presence of active vasculitis on MRI and/or PET/CT (54.5% vs. 58.6 %, p = 1.0), the number of segments with vasculitic findings on MRI (0, IQR 0.0-1.5, vs. 2, IQR 0.0-3.0, p = 0.221) or the highest SUV artery/liver ratio on PET/CT (1.5, IQR 1.4-1.6, vs. 1.3, IQR 1.2-1.6, p = 0.505). The median number of vasculitic segments on PET/CT was 2.5 (IQR 0.5-4.5) in those with vs. 0 (IQR 0.0-1.5, p = 0.085) in those without relapse, and the PET/CT scores 4.5 (IQR 0.75-8.25) vs. 0 (IQR 0.0-3.0, p = 0.172). CONCLUSION: PET/CT or MRI at treatment stop did not predict relapse and may not be suited to guide treatment decisions in patients with LV-GCA in remission.

Correlation of muscle BOLD MRI with transcutaneous oxygen pressure for assessing microcirculation in patients with systemic sclerosis.

PURPOSE: To prospectively compare calf muscle BOLD MRI with transcutaneous oxygen pressure (TcPO2 ) measurement in patients with systemic sclerosis (SSc) and healthy volunteers and thereby get insight into the pathogenesis of vasculopathy in this connective tissue disorder. MATERIALS AND METHODS: Twelve patients with SSc (6 women and 6 men, mean age 53.5 ± 10.0 years) and 12 healthy volunteers (4 men and 8 women, mean age 47 ± 12.1 years) were examined using muscle BOLD MRI and TcPO2. A cuff compression at mid-thigh level was performed to provoke ischemia and reactive hyperemia. BOLD measurements were acquired on a 3 Tesla whole body-scanner in the upper calf region using a multi-echo EPI-sequence with four echo-times (TE: 9/20/31/42 ms) and a repetition time of 2 s. Empirical cross-correlation analysis depending on time lags between BOLD- and TcPO2-measurements was performed. RESULTS: Maximal cross-correlation of BOLD T2*- and TcPO2-measurements was calculated as 0.93 (healthy volunteers) and 0.90 (SSc patients) for a time lag of approximately 40 s. Both modalities showed substantial differences regarding time course parameters between the SSc patients and healthy volunteers. CONCLUSION: Skeletal muscle BOLD MRI correlated very well with TcPO2 . T2* changes seem to reflect reoxygenation deficits in deeper muscle tissue of SSc patients.

The Swiss cohort of elderly patients with venous thromboembolism (SWITCO65+): rationale and methodology.

Venous thromboembolism (VTE) is common and has a high impact on morbidity, mortality, and costs of care. Although most of the patients with VTE are aged ≥65 years, there is little data about the medical outcomes in the elderly with VTE. The Swiss Cohort of Elderly Patients with VTE (SWITCO65+) is a prospective multicenter cohort study of in- and outpatients aged ≥65 years with acute VTE from all five Swiss university and four high-volume non-university hospitals. The goal is to examine which clinical and biological factors and processes of care drive short- and long-term medical outcomes, health-related quality of life, and medical resource utilization in elderly patients with acute VTE. The cohort also includes a large biobank with biological material from each participant. From September 2009 to March 2012, 1,863 elderly patients with VTE were screened and 1003 (53.8%) were enrolled in the cohort. Overall, 51.7% of patients were aged ≥75 years and 52.7% were men. By October 16, 2012, after an average follow-up time of 512 days, 799 (79.7%) patients were still actively participating. SWITCO65+ is a unique opportunity to study short- and long-term outcomes in elderly patients with VTE. The Steering Committee encourages national and international collaborative research projects related to SWITCO65+, including sharing anonymized data and biological samples.

ECG-triggered non-enhanced MR angiography of peripheral arteries in comparison to DSA in patients with peripheral artery occlusive disease.

OBJECT: The purpose of this study was to evaluate peripheral non-enhanced-MRA (NE-MRA) acquired with a 3D Turbo Spin Echo sequence with electrocardiographt (ECG) triggering in comparison to Digital Subtraction Angiography (DSA) as the gold standard in symptomatic peripheral artery occlusive disease (PAOD) patients. MATERIALS AND METHODS: This IRB approved prospective study included 23 PAOD patients from whom three patients had to be excluded. The remaining 20 subjects were included in the analysis (15 male; mean age 62.4 ± 15.3 years). The patients first underwent DSA followed by NE-MRA on a 1.5-T whole body scanner within 24 h after the DSA study. A NATIVE (Non-contrast Angiography of the Arteries and Veins) SPACE (Sampling Perfection with Application Optimized Contrast by using different flip angle Evolution) sequence at four levels (pelvis, upper leg, knee region and lower leg) was acquired. For evaluation purposes, subtracted standardized MIP (maximum intensity projection) images were generated from the NE-MRA data sets. Qualitative assessment of NE-MRA images in reference to the corresponding DSA images, as well as blinded stenosis grading of preselected segments in NE-MRA images were performed by two experienced readers. Image quality in 95 corresponding arterial segments was rated from 1 (good) to 4 (inadequate) directly comparing the NE-MRA with the corresponding DSA segment as the gold standard. Blinded stenosis grading consisted of 66 preselected stenoses rated from 1 (<10 %) to 4 (>90 %) in NE-MRA which were compared to the grade in the corresponding DSA. RESULTS: The mean image quality of NE-MRA in comparison to DSA was 2.7 ± 1.1 (reader 1) and 3.0 ± 1.0 (reader 2). The kappa value indicating interobserver agreement was 0.34; readers 1 and 2 rated the image quality as good in 21 % and 3 %, sufficient in 19 % and 41 %, limited in 29 % and 14 % and inadequate in 31 % and 42 %, respectively. Stenosis graduation revealed significantly higher grades in NE-MRA (reader 1: 3.0 ± 0.7, p < 0.001 and reader 2: 3.1 + 0.8, p < 0.001) compared to DSA (mean value DSA 2.7 ± 0.8). The kappa value indicating interobserver agreement concerning stenosis grading was 0.59. CONCLUSION: NE-MRA revealed a relatively high number of inadequate quality segments. This is in line with recently published comparable studies of the similar SPACE NE-MRA techniques. Further advance of NE-MRA techniques remains desirable for patients with PAOD.

Novel applications of contrast-enhanced ultrasound imaging in vascular medicine.

The use of contrast-enhanced ultrasound (CEUS) for vascular imaging indications has increased dramatically during the last decade. Ultrasound contrast agents are gas-filled microbubbles that are injected into the bloodstream and serve as strict intravascular reflectors of ultrasound waves. Numerous studies have addressed the potential clinical use of CEUS in different vascular fields including the carotid arteries, the abdominal aorta, renal arteries and the kidneys. In this review article we discuss the clinical value of contrast agents in vascular ultrasound by enhancing the vascular lumen, and more important, their role as a tool to deliver high resolution, real-time images of microvascular perfusion. Specifically, CEUS imaging of the carotid artery provides a novel, non-invasive method not only to improve the delineation of the vessel wall, but also for the assessment of the vasa vasorum and the ectopic vascularization of the atherosclerotic plaque (intraplaque neovascularization); probably providing a "window" to risk stratify atherosclerotic lesions and individuals by identifying "vulnerable" plaques prone to rupture causing vascular events. CEUS imaging has also emerged as a novel diagnostic tool in various aortic pathologies and particularly for the detection of endoleaks following endovascular treatment of abdominal aortic aneurysms. It is also a valuable tool for the assessment of the tissue perfusion in native and transplanted kidneys providing information on perfusion deficits of the parenchyma. Furthermore, a real-time CEUS method has recently been developed to assess the skeletal muscle microcirculation which could be used to study patients with peripheral arterial occlusive disease or diabetic microangiopathy. In the future, the use of targeted microbubbles could further enhance and expand the diagnostic capabilities of current vascular ultrasound imaging by detecting specific molecular processes that play a role in the pathophysiology of vascular disease.