MR angiography of infrapopliteal arteries in patients with peripheral arterial occlusive disease by using Gadofosveset at 3.0 T: diagnostic accuracy compared with selective DSA

To prospectively compare the diagnostic accuracy of steady-state, high-spatial-resolution magnetic resonance (MR) angiography of the lower leg, performed with a blood pool contrast agent, with selective digital subtraction angiography (DSA) as the reference standard in patients with symptomatic peripheral arterial disease.

Breathing manoeuvre-dependent changes in myocardial oxygenation in healthy humans.

AIMS CO₂ is an intrinsic vasodilator for cerebral and myocardial blood vessels. Myocardial vasodilation without a parallel increase of the oxygen demand leads to changes in myocardial oxygenation. Because apnoea and hyperventilation modify blood CO₂, we hypothesized that voluntary breathing manoeuvres induce changes in myocardial oxygenation that can be measured by oxygenation-sensitive cardiovascular magnetic resonance (CMR). METHODS AND RESULTS Fourteen healthy volunteers were studied. Eight performed free long breath-hold as well as a 1- and 2-min hyperventilation, whereas six aquatic athletes were studied during a 60-s breath-hold and a free long breath-hold. Signal intensity (SI) changes in T₂*-weighted, steady-state free precession, gradient echo images at 1.5 T were monitored during breathing manoeuvres and compared with changes in capillary blood gases. Breath-holds lasted for 35, 58 and 117 s, and hyperventilation for 60 and 120 s. As expected, capillary pCO₂ decreased significantly during hyperventilation. Capillary pO₂ decreased significantly during the 117-s breath-hold. The breath-holds led to a SI decrease (deoxygenation) in the left ventricular blood pool, while the SI of the myocardium increased by 8.2% (P = 0.04), consistent with an increase in myocardial oxygenation. In contrast, hyperventilation for 120 s, however, resulted in a significant 7.5% decrease in myocardial SI/oxygenation (P = 0.02). Change in capillary pCO₂ was the only independently correlated variable predicting myocardial oxygenation changes during breathing manoeuvres (r = 0.58, P < 0.01). CONCLUSION In healthy individuals, breathing manoeuvres lead to changes in myocardial oxygenation, which appear to be mediated by CO₂. These changes can be monitored in vivo by oxygenation-sensitive CMR and thus, may have value as a diagnostic tool.

Serial [18F]-fluoromisonidazole PET during radiochemotherapy for locally advanced head and neck cancer and its correlation with outcome.

PURPOSE The aim was to assess changes of tumour hypoxia during primary radiochemotherapy (RCT) for head and neck cancer (HNC) and to evaluate their relationship with treatment outcome. MATERIAL AND METHODS Hypoxia was assessed by FMISO-PET in weeks 0, 2 and 5 of RCT. The tumour volume (TV) was determined using FDG-PET/MRI/CT co-registered images. The level of hypoxia was quantified on FMISO-PET as TBRmax (SUVmaxTV/SUVmean background). The hypoxic subvolume (HSV) was defined as TV that showed FMISO uptake ⩾1.4 times blood pool activity. RESULTS Sixteen consecutive patients (T3-4, N+, M0) were included (mean follow-up 31, median 44months). Mean TBRmax decreased significantly (p<0.05) from 1.94 to 1.57 (week 2) and 1.27 (week 5). Mean HSV in week 2 and week 5 (HSV2=5.8ml, HSV3=0.3ml) were significantly (p<0.05) smaller than at baseline (HSV1=15.8ml). Kaplan-Meier plots of local recurrence free survival stratified at the median TBRmax showed superior local control for less hypoxic tumours, the difference being significant at baseline and after 2weeks (p=0.031, p=0.016). CONCLUSIONS FMISO-PET documented that in most HNC reoxygenation starts early during RCT and is correlated with better outcome.

Added value of coronary artery calcium score as an adjunct to gated SPECT for the evaluation of coronary artery disease in an intermediate-risk population

The coronary artery calcium (CAC) score is a readily and widely available tool for the noninvasive diagnosis of atherosclerotic coronary artery disease (CAD). The aim of this study was to investigate the added value of the CAC score as an adjunct to gated SPECT for the assessment of CAD in an intermediate-risk population. METHODS: Seventy-seven prospectively recruited patients with intermediate risk (as determined by the Framingham Heart Study 10-y CAD risk score) and referred for coronary angiography because of suspected CAD underwent stress (99m)Tc-tetrofosmin SPECT myocardial perfusion imaging (MPI) and CT CAC scoring within 2 wk before coronary angiography. The sensitivity and specificity of SPECT alone and of the combination of the 2 methods (SPECT plus CAC score) in demonstrating significant CAD (>/=50% stenosis on coronary angiography) were compared. RESULTS: Forty-two (55%) of the 77 patients had CAD on coronary angiography, and 35 (45%) had abnormal SPECT results. The CAC score was significantly higher in subjects with perfusion abnormalities than in those who had normal SPECT results (889 +/- 836 [mean +/- SD] vs. 286 +/- 335; P < 0.0001). Similarly, with rising CAC scores, a larger percentage of patients had CAD. Receiver-operating-characteristic analysis showed that a CAC score of greater than or equal to 709 was the optimal cutoff for detecting CAD missed by SPECT. SPECT alone had a sensitivity and a specificity for the detection of significant CAD of 76% and 91%, respectively. Combining SPECT with the CAC score (at a cutoff of 709) improved the sensitivity of SPECT (from 76% to 86%) for the detection of CAD, in association with a nonsignificant decrease in specificity (from 91% to 86%). CONCLUSION: The CAC score may offer incremental diagnostic information over SPECT data for identifying patients with significant CAD and negative MPI results.

Cardiac sodium channel NaV1.5 distribution in myocytes via interacting proteins: the multiple pool model

The cardiac sodium current (INa) is responsible for the rapid depolarization of cardiac cells, thus allowing for their contraction. It is also involved in regulating the duration of the cardiac action potential (AP) and propagation of the impulse throughout the myocardium. Cardiac INa is generated by the voltage-gated Na(+) channel, NaV1.5, a 2016-residue protein which forms the pore of the channel. Over the past years, hundreds of mutations in SCN5A, the human gene coding for NaV1.5, have been linked to many cardiac electrical disorders, including the congenital and acquired long QT syndrome, Brugada syndrome, conduction slowing, sick sinus syndrome, atrial fibrillation, and dilated cardiomyopathy. Similar to many membrane proteins, NaV1.5 has been found to be regulated by several interacting proteins. In some cases, these different proteins, which reside in distinct membrane compartments (i.e. lateral membrane vs. intercalated disks), have been shown to interact with the same regulatory domain of NaV1.5, thus suggesting that several pools of NaV1.5 channels may co-exist in cardiac cells. The aim of this review article is to summarize the recent works that demonstrate its interaction with regulatory proteins and illustrate the model that the sodium channel NaV1.5 resides in distinct and different pools in cardiac cells. This article is part of a Special Issue entitled: Cardiomyocyte Biology: Cardiac Pathways of Differentiation, Metabolism and Contraction.

Brain areas involved in medial temporal lobe seizures: a principal component analysis of ictal SPECT data

The study describes brain areas involved in medial temporal lobe (mTL) seizures of 12 patients. All patients showed so-called oro-alimentary behavior within the first 20 s of clinical seizure manifestation characteristic of mTL seizures. Single photon emission computed tomography (SPECT) images of regional cerebral blood flow (rCBF) were acquired from the patients in ictal and interictal phases and from normal volunteers. Image analysis employed categorical comparisons with statistical parametric mapping and principal component analysis (PCA) to assess functional connectivity. PCA supplemented the findings of the categorical analysis by decomposing the covariance matrix containing images of patients and healthy subjects into distinct component images of independent variance, including areas not identified by the categorical analysis. Two principal components (PCs) discriminated the subject groups: patients with right or left mTL seizures and normal volunteers, indicating distinct neuronal networks implicated by the seizure. Both PCs were correlated with seizure duration, one positively and the other negatively, confirming their physiological significance. The independence of the two PCs yielded a clear clustering of subject groups. The local pattern within the temporal lobe describes critical relay nodes which are the counterpart of oro-alimentary behavior: (1) right mesial temporal zone and ipsilateral anterior insula in right mTL seizures, and (2) temporal poles on both sides that are densely interconnected by the anterior commissure. Regions remote from the temporal lobe may be related to seizure propagation and include positively and negatively loaded areas. These patterns, the covarying areas of the temporal pole and occipito-basal visual association cortices, for example, are related to known anatomic paths.

ABO blood group incompatible haematopoietic stem cell transplantation and xenograft rejection

The current organ shortage in transplantation medicine stimulates the exploration of new strategies to expand the donor pool including the utilisation of living donors, ABO-incompatible grafts, and xenotransplantation. Preformed natural antibodies (Ab) such as anti-Gal or anti-A/B Ab mediate hyperacute graft rejection and thus represent a major hurdle to the employment of such strategies. In contrast to solid organ transplantation (SOT), ABO blood group incompatibilities are of minor importance in haematopoietic stem cell transplantation (HSCT). Thus, ABO incompatible HSCT may serve as an in vivo model to study carbohydrate antigen (Ag)-mismatched transplantations such as ABO-incompatible SOT or the effect of preformed Ab against Gal in xenotransplantation. This mini-review summarises our clinical and experimental studies performed with the support of the Swiss National Science Foundation program on Implants and Transplants (NFP-46). Part 1 describes data on the clinical outcome of ABO-incompatible HSCT, in particular the incidence of several immunohaematological complications, acute graft-versus-host-disease (GvHD), and the overall survival. Part 2 summarises the measurements of anti-A/B Ab in healthy blood donors and ABO-incompatible HSCT using a novel flow cytometry based method and the potential mechanisms responsible for the loss of anti-A/B Ab observed following minor ABO-incompatible HSCT, ie the occurrence of humoral tolerance. Part 3 analyses the potential of eliminating Gal expression as well as specific complement inhibitors such as dextran sulfate and synthetic tyrosine analogues to protect porcine endothelial cells from xenoreactive Ab-mediated damage in vitro and in a hamster-to-rat heart transplantation model. In conclusion, due to similarities of the immunological hurdles of ABO incompatible transplantations and xenotransplantation, the knowledge obtained from both fields might lead to new strategies to overcome humoral rejection in transplantation.

Assessment of splanchnic blood flow using magnetic resonance imaging

BACKGROUND AND AIMS: The splanchnic circulation has an important function in the body under both physiological and pathophysiological conditions. Despite its importance, no reliable noninvasive procedures for estimating splanchnic circulation have been established. The aim of this study was to evaluate MRI as a tool for assessing intra-abdominal blood flows of the aorta, portal vein (VPO) and the major intestinal and hepatic vessels. METHODS: In nine healthy volunteers, the proximal aorta (AOP) and distal abdominal aorta (AOD), superior mesenteric artery (SAM), celiac trunk (CTR), hepatic arteries (common and proper hepatic arteries, AHC and AHP, respectively), and VPO were localized on contrast-enhanced magnetic resonance angiography images. Volumetric flow was measured using a two-dimensional cine echocardiogram-gated phase contrast technique. Measurements were taken before and 30 min after continuous intravenous infusion of somatostatin (250 microg/h) and were independently evaluated by two investigators. RESULTS: Blood flow measured by MRI in the VPO, SAM, AOP, AHP, and CTR significantly decreased after drug infusion. Flows in the AOD and AHC showed a tendency to decrease (P>0.05). Interrater agreement on flows in MRI was very good for large vessels (VPO, AOP, and AOD), with a concordance correlation coefficient of 0.94, as well as for smaller vessels such as the CTR, AHC, AHP, and SAM (concordance correlation coefficient =0.78). CONCLUSION: Somatostatin-induced blood flow changes in the splanchnic region were reliably detected by MRI. MRI may be useful for the noninvasive assessment of blood flow changes in the splanchnic region.