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.

Correlation of carotid artery atherosclerotic lesion echogenicity and severity at standard US with intraplaque neovascularization detected at contrast-enhanced US.

PURPOSE: To correlate echogenicity and severity of atherosclerotic carotid artery lesions at standard ultrasonography (US) with the degree of intraplaque neovascularization at contrast material-enhanced (CE) US. MATERIALS AND METHODS: This HIPAA-compliant study was approved by the local ethics committee, and all patients provided informed consent. A total of 175 patients (113 [65%] men, 62 [35%] women; mean age, 67 years ± 10 [standard deviation]) underwent standard and CE US of the carotid artery. Lesion echogenicity (class I to IV), degree of stenosis, and maximal lesion thickness were evaluated for each documented atherosclerotic lesion. The degree of intraplaque neovascularization at CE US was categorized as absent (grade 1), moderate (grade 2), or extensive (grade 3). Correlation of neovascularization with echogenicity, degree of stenosis, and maximal lesion thickness was made by using Spearman ρ and χ(2) test for trend. RESULTS: In a total of 293 atherosclerotic lesions, echogenicity was inversely correlated with grade of intraplaque neovascularization (ρ = -0.199, P < .001). More echolucent lesions had a higher degree of neovascularization compared with more echogenic ones (P < .001). The degree of stenosis was significantly correlated with grade of intraplaque neovascularization (ρ = 0.157, P = .003). Lesions with higher degree of stenosis had higher grade of neovascularization (P = .008), and maximal lesion thickness increased with the grade of neovascularization (P < .001) and was significantly correlated with grade of neovascularization (ρ = 0.233, P < .001). CONCLUSION: Neovascularization visualized with CE US correlates with lesion severity and with morphologic features of plaque instability, contributing to the concept that more vulnerable plaques are more likely to have a greater degree of neovascularization. Therefore, CE US may be a valuable tool for further risk stratification of echolucent atherosclerotic lesions and carotid artery stenosis of different degrees. SUPPLEMENTAL MATERIAL: http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.10101008/-/DC1.

Vasa vasorum and plaque neovascularization on contrast-enhanced carotid ultrasound imaging correlates with cardiovascular disease and past cardiovascular events.

BACKGROUND AND PURPOSE: Histological data associate proliferation of adventitial vasa vasorum and intraplaque neovascularization with vulnerable plaques represented by symptomatic vascular disease. In this observational study, the presence of carotid intraplaque neovascularization and adventitial vasa vasorum were correlated with the presence and occurrence of cardiovascular disease (CVD) and events (CVE). METHODS: The contrast-enhanced carotid ultrasound examinations of 147 subjects (mean age 64+/-11 years, 61% male) were analyzed for the presence of intraluminal plaque, plaque neovascularization (Grade 1=absent; Grade 2=present), and degree of adventitial vasa vasorum (Grade 1=absent, Grade 2=present). These observations were correlated with preexisting cardiovascular risk factors, presence of CVD, and history of CVE (myocardial infarction and transient ischemic attack/stroke). RESULTS: The presence of intraluminal carotid plaque was directly correlated to cardiovascular risk factors, CVD, and CVE (P<0.05). Adventitial vasa vasorum Grade 2 was associated with significant more subjects with CVD than vasa vasorum Grade 1 (73 versus 54%, P=0.029). Subjects with intraplaque neovascularization Grade 2 had significantly more often a history of CVE than subjects with intraplaque neovascularization Grade 1 (38 versus 20%, P=0.031). Multivariate logistic regression analysis revealed that presence of plaque was significantly associated with CVD (odds ratio 4.7, 95% CI 1.6 to 13.8) and intraplaque neovascularization grade 2 with CVE (odds ratio 4.0, 95% CI 1.3 to 12.6). CONCLUSIONS: The presence and degree of adventitial vasa vasorum and plaque neovascularization were directly associated with CVD and CVE in a retrospective study of 147 patients undergoing contrast-enhanced carotid ultrasound.

Vascular involvement in patients with giant cell arteritis determined by duplex sonography of 2x11 arterial regions.

OBJECTIVE: To define the specificity and extent of duplex sonography (DS) findings suggestive of vessel wall inflammation in patients with giant cell arteritis (GCA). METHODS: Patients admitted between December 2006 and April 2009 to the University Hospital Basel with a suspicion of GCA were eligible for the study. DS of 2x11 arterial regions was performed in all study participants, and American College of Rheumatology criteria were applied to classify patients into GCA or non-GCA groups. RESULTS: GCA was diagnosed in 38 of the 72 participants (53%). A DS pattern suggestive of vessel wall inflammation was not observed in any of the patients in the non-GCA group but, in 21 of the 38 patients with GCA (55%), DS signs suggestive of vessel wall inflammation of > or =1 vessel region were detected. In 12 of the 38 patients with GCA (32%), DS signs of large vessel vasculitis (LVV) were found in > or =1 vessel region(s) of both upper and lower limb vessels. Follow-up DS was performed 6 months after the baseline examination in 9 of the 12 patients with LVV and showed the persistence of most findings despite normalised signs of systemic inflammation. CONCLUSION: DS detects changes in the vessel wall that appear to be specific for GCA; they can be present in upper and lower limb arteries of patients with GCA. Surprisingly, DS-detectable LVV and signs of systemic inflammation are largely dissociated.

Rapid adaptation of the intrarenal resistance index after living donor kidney transplantation.

BACKGROUND: Limited data exist concerning changes of renal perfusion directly after kidney transplantation. Colour-coded duplex sonography is the accepted method to assess kidney perfusion after transplantation. A widely used, although unspecific, Doppler parameter is the intrarenal resistance index (RI). The aim of this study was to clarify the influence of different patient- and procedure-related factors on RI before and immediately after living kidney transplantation. METHODS: In a prospective study, 80 living kidney transplantation donor-recipient pairs were included. RI was measured in the donor 1 to 3 days before nephrectomy and in the recipient during the first hour after transplantation to examine the influence of age, heart rate, duration of cold and warm ischaemia time and immunosuppressive medications. RESULTS: Mean RI did not differ between donors and recipients. RI correlated with age, both in donors (r = 0.58, P < 0.001) and recipients (r = 0.39, P < 0.001). In recipients, 10 or more years younger than their donors (n = 24), an average decrease of 0.05 in RI compared to the donors' value was observed (P = 0.01). Heart rate, cold and warm ischaemia time and immunosuppressive medications had no influence on the recipient RI. In patients with delayed graft function, a significant increase in RI within 14 days was observed. However, the initial RI was not predictive of graft function. CONCLUSIONS: The transplanted kidney seems to be able to adjust its RI within a short time despite several potential harmful factors that can occur during the transplantation.

Assessment of cutaneous microcirculation in unaffected skin regions by transcutaneous oxygen saturation monitoring and Laser Doppler flowmetry in systemic sclerosis.

We assessed the cutaneous microcirculatory reactivity of a clinically unaffected skin region in patients with systemic sclerosis (SSc) compared to healthy controls by measuring transcutaneous oxygen saturation (TcPO2) and Laser Doppler flowmetry (LDF).Twelve consecutive patients with SSc and twelve healthy controls were subjected to TcPO2 monitoring and LDF during cuff-induced ischemia and reactive hyperemia in order to measure the skin oxygen tension and the microcirculatory blood flow. Mean minimal and maximal values of oxygen tension and blood flow, time to peak (TTP), and declining slopes after peaking (slope) were compared between patients with SSc and controls.Compared to the controls, TcPO2 values in SSc were similar during ischemia and diminished during reactive hyperemia, with longer TTP, and a slower return to baseline (-60% vs. -58% , p = 1.000, +76% vs. +210% , p = 0.047, 137 s vs. 108 s, p = 0.028, -0.009% /s vs. -0.019% /s, p = 0.021, respectively). LDF values, however, did not differ significantly between patients with SSc and controls.Unaffected skin regions of SSc patients showed a significantly diminished postischemic vasodilatory reactivity when assessed by TcPO2 monitoring, but not by LDF, indicating that vasculopathy may represent an early mechanism in the onset of skin sclerosis. TcPO2 measurement may help to detect changes in the microcirculation in SSc with no skin affection.

Effect of aspirin versus clopidogrel on walking exercise performance in intermittent claudication-a double-blind randomized multicenter trial.

BACKGROUND: This study sought to determine possible effects of different antiplatelet therapies on walking exercise performance in intermittent claudication. Aspirin, in contrast to clopidogrel, interferes with processes that increase collateral conductance in an ischemic animal model. METHODS AND RESULTS: Patients with stable intermittent claudication were recruited from 21 centers in Switzerland and Germany and randomized to either aspirin or clopidogrel treatment. They participated in a 3-month rehabilitation program (electronically monitored, home-based, 1-hour daily walking sessions at a speed of approximately 120 steps/min). Walking distance was assessed by treadmill tests (3.2 km/h; 12% grade) at baseline and after 12 weeks. A total of 229 of 259 patients with a mean age of 66.2±7.7 years completed the study according to the protocol. A total of 24.5% were females, 20.1% diabetics, and 85.6% were active/ex-smokers. The baseline characteristics were a median (interquartile range) ankle/brachial index of 0.69 (0.57±0.8), an initial claudication distance (ICD) of 98 m (70 to 151 m), and an absolute claudication distance (ACD) of 162 m (113 to 302 m). Training resulted in a median increase of initial claudication distance by 33.5 m (33.3%) in the clopidogrel group and 29 m (33.9%) in the aspirin group. The values for absolute claudication distance were 60.5 m (34.9%) and 75 m (35.3%), respectively (p(ICD)=0.42 and p(ACD)=0.66). CONCLUSIONS: Treatment with aspirin did not show a difference in initial claudication distance or absolute claudication distance improvements compared with clopidogrel after a 3-month walking rehabilitation program. (J Am Heart Assoc. 2012;1:51-56.) CLINICAL TRIAL REGISTRATION: URL: http://www.ClinicalTrials.gov. Unique identifier: NCT00189618, URL: https://EudraCT.ema.europa.eu, Unique identifier: 2004-005041-35.

Central venous pressure and impaired renal function in patients with acute heart failure.

AIMS: To determine the relationship between central venous pressure (CVP) and renal function in patients with acute heart failure (AHF) presenting to the emergency department. METHODS AND RESULTS: Central venous pressure was determined non-invasively using compression sonography in 140 patients with AHF at presentation. Worsening renal function (WRF) was defined as an increase in serum creatinine ≥ 0.3 mg/dL during hospitalization. In the study cohort [age 77 ± 12 years, B-type natriuretic peptide 1862 ± 1564 pg/mL, left ventricular ejection fraction 40 ± 15%, estimated glomerular filtration rate (eGFR) 58 ± 28 mL/min, and CVP 13.2 ± 6.9 cmH(2)O], 51 patients (36%) developed WRF. No significant association between CVP at presentation or discharge and concomitant eGFR (r = 0.005, P = 0.419 and r = 0.013, P = 0.313, respectively) was observed. However, in patients with systolic blood pressure (SBP) <110 mmHg and concomitant high CVP (>15 cmH(2)O), eGFR was significantly lower at presentation and discharge (29 ± 17 vs. 47 ± 19 mL/min/1.73 m(2), P = 0.039 and 26 ± 10 vs. 53 ± 26 mL/min/1.73 m(2), P = 0.013, respectively). Central venous pressure at presentation and at discharge did not differ between patients with or without in-hospital WRF (12.6 ± 7.2 vs. 13.5 ± 6.7 cmH(2)O, P = 0.503 and 7.4 ± 6.5 vs. 7.7 ± 5.7 cmH(2)O, P = 0.799, respectively) (receiver-operating characteristic analysis 0.543, P = 0.401 and 0.531, P = 0.625, respectively). However, patients with CVP in the lowest tertile (<10 cmH(2)O) at presentation were more likely to develop WRF within the first 24 h than patients with CVP in the highest tertile (>15 cmH(2)O) (18 vs. 4%, P = 0.046). CONCLUSION: In AHF, combined low SBP and high CVP predispose to lower eGFR. However, lower CVP may also be associated with short-term WRF. The pathophysiology of WRF and the role of CVP seem to be more complex than previously thought.

Central venous pressure at emergency room presentation predicts cardiac rehospitalization in patients with decompensated heart failure.

AIMS: To investigate the relationship between central venous pressure (CVP) at presentation to the emergency room (ER) and the risk of cardiac rehospitalization and mortality in patients with decompensated heart failure (DHF). METHODS AND RESULTS: Central venous pressure was determined non-invasively using high-resolution compression sonography at presentation in 100 patients with DHF. Cardiac hospitalizations and cardiac and all-cause mortality were assessed as a function of continuous CVP levels and predefined CVP categories (low <6 cm H(2)O, intermediate 6-23 cm H(2)O, and high >23 cm H(2)O). Endpoints were adjudicated blinded to CVP. At presentation, mean age was 78 +/- 11 years, 60% of patients were male, mean B-type natriuretic peptide level was 1904 +/- 1592 pg/mL, and mean CVP was 13.7 +/- 7.0 cm H(2)O (range 0-33). During follow-up (median 12 months), 25 cardiac rehospitalizations, 26 cardiac deaths, and 7 non-cardiac deaths occurred. Univariate and stepwise multivariate Cox regression analysis revealed an independent relationship between CVP and cardiac rehospitalization (HR 1.09, 95% CI 1.01-1.18, P = 0.034). Kaplan-Meier analyses confirmed a stepwise increase in cardiac rehospitalization for low-to-high CVP (log-rank test P = 0.015). No association between CVP and (cardiac) mortality was detectable. CONCLUSION: Central venous pressure at ER presentation in patients with DHF is an independent predictor of cardiac rehospitalization but not of cardiac and all-cause mortality.

Non-invasive central venous pressure measurement by compression ultrasound--a step into real life.

AIM OF THE STUDY: Information on central venous pressure (CVP) is helpful in clinical situations like cardiac failure and sepsis. Compression ultrasound (CU) of a forearm vein has been shown to be a reliable method for CVP measurement when assessed by experienced personal under study conditions. To test the hypothesis, that CU can be reliably used for CVP measurement after a training program and using a portable ultrasound system, we investigated feasibility and accuracy of CU, comparing the results of vascular experts vs. trainees as well as high-end vs. a portable ultrasound system. METHODS: CU with non-invasive CVP measurement (CVP(ni)) was performed by four investigators in 50 patients of an intensive care unit and compared with invasive CVP measurement (CVP(i)). RESULTS: Feasibility was between 88 and 92% in the different investigator groups. CVP(ni) measurement showed a significant linear correlation (r=0.58-0.68; p<0.001) with CVP(i) in all groups. Mean difference between CVP(i) and CVP(ni) was 2.4+/-3.1mmHg and similar between the investigators. No differences were observed between measurements done by vascular experts and trainees, as well as between high-end and portable ultrasound systems. Further we demonstrated, that CU is able to detect changes in CVP during the respiratory cycle. CONCLUSIONS: After a training program CU can be used by non-vascular clinician for reliable CVP measurement with good quality portable systems. Furthermore, respiratory changes in CVP are detectable by CU. These data suggest CU to be an efficient method for measuring CVP under real life conditions.

Effect of prolonged treatment with compression stockings to prevent post-thrombotic sequelae: a randomized controlled trial.

OBJECTIVE: Compression stockings are widely applied after acute proximal deep vein thrombosis, but their efficacy in preventing the post-thrombotic syndrome remains controversial. This study assessed the effect of prolonged compression therapy after a standard treatment of 6 months after acute deep vein thrombosis. METHODS: Of 900 patients screened, we randomly allocated 169 patients with a first or recurrent proximal deep vein thrombosis after receiving 6 months of standard treatment to wear compression stockings or not. Primary efficacy analysis was performed on the end point of emerging skin changes (C4-C6 according to the CEAP classification). Secondary analysis was done on symptoms associated with post-thrombotic syndrome. All analyses were done according to the intention-to-treat principle. RESULTS: The primary end point occurred in 11 patients (13.1%) in the treatment group compared with 17 (20.0%) in the control group (hazard ratio [HR], 0.60; 95% confidence interval [CI], 0.28-1.28; P = .19). Mean follow-up was 3.2 years and 2.9 years, respectively. Five additional patients in the control group required compression therapy owing to post-thrombotic signs and symptoms not included in the primary end point. No venous ulceration was observed in either group. Within subgroup analyses of the primary end point, we observed a large sex-specific difference between women (HR, 0.11; 95% CI, 0.02-0.91) and men (HR, 1.07; 95% CI, 0.42-2.73). Symptom relief was significant in favor of compression treatment during the first year but not thereafter. CONCLUSION: Prolonged compression therapy after proximal deep vein thrombosis significantly reduces symptoms and may prevent post-thrombotic skin changes. Whether these findings translate to the prevention of advanced disease states with ulcerations remains unclear.

Noninvasive central venous pressure measurement by controlled compression sonography at the forearm.

OBJECTIVES: We sought to validate a new noninvasive technique to determine central venous pressure (CVP) using high-resolution compression sonography. BACKGROUND: Information concerning CVP is crucial in clinical situations, including cardiac failure, volume overload, and sepsis. The measurement of CVP, however, requires puncture of a vein with attendant risk of complication. METHODS: After a proof-of-concept study in healthy subjects, a prospective blinded evaluation was performed comparing CVP measurement using a central venous catheter with measurement using compression sonography in critically ill (intensive care unit) patients. RESULTS: In healthy subjects with experimentally induced venous hypertension with a wide range of pressure values, a strong correlation (r = 0.95; p < 0.001) between noninvasive and invasive peripheral venous pressure at the forearm was shown. High interobserver agreement with an intraclass correlation coefficient of 0.988 shows excellent reliability of the system. Noninvasive peripheral venous pressure measurement at the forearm showed a good correlation with CVP in 50 intensive care unit patients with the forearm positioned both below heart level (r = 0.84; p < 0.001) and at heart level (r = 0.85; p < 0.001). The mean difference between invasive and noninvasive measurement was negligible (-0.1 +/- 3.5 cm H2O and -0.7 +/- 3.4 cm H2O, respectively). CONCLUSIONS: Controlled-compression sonography is a valuable tool for measuring venous pressure in peripheral veins and allows reliable indirect assessment of CVP without intravenous catheterization.

Calf muscles imaged at BOLD MR: correlation with TcPO2 and flowmetry measurements during ischemia and reactive hyperemia--initial experience.

PURPOSE: To prospectively compare the blood oxygen level-dependent (BOLD) magnetic resonance (MR) signal intensity of calf muscle during ischemia and reactive hyperemia with laser Doppler flowmetry (LDF) and transcutaneous oxygen pressure (TcPo2) measurements, two parameters routinely used to evaluate peripheral arterial occlusive disease. MATERIALS AND METHODS: The study was institutional review board approved; all volunteers gave informed consent. Fifteen healthy volunteers (eight male, seven female; mean age, 33.0 years +/- 6.1 [standard deviation]) underwent LDF, TcPo2 measurement, and BOLD MR imaging of the calf during ischemia and reactive hyperemia. The BOLD signal intensity of the gastrocnemius muscle was measured at 1.5-T single-shot multiecho gradient-echo echo-planar imaging. Time to half ischemia minimum (THIM), time to half hyperemia peak (THHP), and time to peak (TTP) after cuff deflation were measured with each method. Correlation coefficients (CCs) for associations of BOLD response with LDF and TcPo2 time courses were calculated. Student t testing of key BOLD MR, LDF, and TcPo2 measurement parameters was performed. RESULTS: During ischemia, normalized LDF and TcPo2 measurements decreased similarly to BOLD MR signal intensity (CCs: 0.86 and 0.96 for associations with LDF and TcPo2 measurements, respectively). Mean THIM values were 136.0, 82.5, and 121.3 seconds for BOLD MR, LDF (P < .01), and TcPo2 (P > .05) measurements, respectively. During early reactive hyperemia, LDF and TcPo2 measurements increased rapidly to peak values, similarly to BOLD MR signal intensity (CCs: 0.81 and 0.78, respectively). Mean THHP values were 26.0, 12.5, and 44.0 seconds for BOLD MR, LDF (P < .01), and TcPo2 (P < .01) measurements, respectively. Mean TTP values were 48.7, 47.5, and 98.0 seconds for BOLD MR, LDF (P > .05), and TcPo2 (P < .01) measurements, respectively. CONCLUSION: BOLD MR imaging of calf muscles-depending on underlying key parameters-has moderate to good correlation with LDF and TcPo2 measurements during ischemia and reactive hyperemia.

Intraarterial versus IV gadolinium injections for MR angiography: quantitative and qualitative assessment of the infrainguinal arteries.

OBJECTIVE: Our purpose was to quantitatively and qualitatively compare 3D intraarterial (IA) gadolinium-enhanced MR angiography (IA MRA) versus the standard of reference of MR angiography, 3D IV gadolinium-enhanced MR angiography (IV MRA), in patients with peripheral arterial occlusive disease (PAOD) for use during catheter-based MR-guided endovascular interventions. CONCLUSION: IA MRA provides image quality of the infrainguinal arteries in PAOD patients comparable to IV MRA with a significantly improved assessment of the infrapopliteal arteries due to reduced venous contamination. Further benefits of IA MRA include usage of only very low doses of gadolinium and simplified bolus timing.

Lower extremity: low-dose contrast agent intraarterial MR angiography in patients--initial results.

Institutional review board approval and patient consent were obtained. A low-dose injection protocol for intraarterial three-dimensional (3D) gadolinium-enhanced magnetic resonance (MR) angiography was derived from femoral flow phantom studies and prospectively evaluated in patients with peripheral arterial occlusive disease (PAOD). All MR angiograms were obtained at 1.5 T with a T1-weighted gradient-echo sequence. MR angiograms of a gadolinium dilution series (0.8-200.0 mmol/L) were acquired in a femoral phantom at different flow rates. Signal-to-noise ratios (SNRs) above the 75% threshold of the measured maximum were considered optimal. The lowest optimal concentration was injected intraarterially in nine patients to obtain 3D MR angiograms of the thigh and calf station. Contrast-to-noise ratios (CNRs) were calculated for four arterial segments. The low optimal concentration of 50 mmol/L (20-mL bolus volume), about 5% of the total permissible dose, showed SNRs larger than the 75% threshold in the phantom study. In patients, this concentration led to high-spatial-resolution angiograms with mean CNRs of 70.0 +/- 14.5 (+/- standard deviation) for the superficial femoral artery and 47.5 +/- 13.4 at the infrapopliteal level. Low-dose contrast agent intraarterial 3D MR angiography showed high arterial enhancement, enabling assessment of lower extremity arteries in patients with PAOD and multiple injections--a crucial precondition for MR-guided endovascular interventions.