Optogenetic manipulation of cardiac electrical dynamics using sub-threshold illumination: dissecting the role of cardiac alternans in terminating rapid rhythms.

Cardiac action potential (AP) shape and propagation are regulated by several key dynamic factors such as ion channel recovery and intracellular Ca2+ cycling. Experimental methods for manipulating AP electrical dynamics commonly use ion channel inhibitors that lack spatial and temporal specificity. In this work, we propose an approach based on optogenetics to manipulate cardiac electrical activity employing a light-modulated depolarizing current with intensities that are too low to elicit APs (sub-threshold illumination), but are sufficient to fine-tune AP electrical dynamics. We investigated the effects of sub-threshold illumination in isolated cardiomyocytes and whole hearts by using transgenic mice constitutively expressing a light-gated ion channel (channelrhodopsin-2, ChR2). We find that ChR2-mediated depolarizing current prolongs APs and reduces conduction velocity (CV) in a space-selective and reversible manner. Sub-threshold manipulation also affects the dynamics of cardiac electrical activity, increasing the magnitude of cardiac alternans. We used an optical system that uses real-time feedback control to generate re-entrant circuits with user-defined cycle lengths to explore the role of cardiac alternans in spontaneous termination of ventricular tachycardias (VTs). We demonstrate that VT stability significantly decreases during sub-threshold illumination primarily due to an increase in the amplitude of electrical oscillations, which implies that cardiac alternans may be beneficial in the context of self-termination of VT.

Requirement of MyD88 and Fas pathways for the efficacy of allergen-free immunotherapy.

BACKGROUND: We have shown that mycobacterial antigens and CpG oligodeoxynucleotides downmodulate airway allergic inflammation by mechanisms dependent on T-cell activation. Here, we investigated the participation of the innate response, particularly the role of MyD88 adaptor, and Fas molecules in the effectiveness of DNA-HSP65 or CpG/culture filtrated proteins (CFP) immunotherapy. METHODS: Mice sensitized and challenged with Der p 1 allergen were treated with DNA-HSP65, CpG/CFP, or with adoptively transferred cells from immunized mice. The treatment efficacy was assessed by evaluating eosinophil recruitment, antibody, and cytokine production. RESULTS: In addition to downregulating the Th2 response, DNA-HSP65 and CpG/CFP promoted IL-10 and IFN-γ production. Adoptive transfer of cells from mice immunized with DNA-HSP65 or CpG/CFP to allergic recipients downmodulated the allergic response. Notably, transfer of cells from DNA-HSP65- or CpG/CFP-immunized MyD88(-/-) mice failed to reduce allergy. Additionally, for effective reduction of allergy by cells from CpG/CFP-immunized mice, Fas molecules were required. Although DNA-HSP65 or CpG/CFP immunization stimulated antigen-specific production of IFN-γ and IL-10, the effect of DNA-HSP65 was associated with IL-10 while CpG/CFP was associated with IFN-γ. Moreover, after stimulation with mycobacterial antigens plus Der p 1 allergen, cells from mite-allergic patients with asthma exhibited similar patterns of cytokine production as those found in the lung of treated mice. CONCLUSIONS: This study provides new insights on the mechanisms of allergen-free immunotherapy by showing that both DNA-HSP65 and CpG/CFP downregulated house dust mite-induced allergic airway inflammation via distinct pathways that involve not only induction of mycobacterial-specific adaptive responses but also signaling via MyD88 and Fas molecules.

Mycobacterium bovis BCG killed by extended freeze-drying induces an immunoregulatory profile and protects against atherosclerosis.

OBJECTIVES: Atherosclerosis is an inflammatory disease of the arterial wall that leads to myocardial infarction and stroke. Regulatory T cells (Tregs) and IL-10 exert significant anti-atherogenic effects in experimental models of atherosclerosis by modulating vascular inflammation. We have previously shown that Mycobacterium bovis BCG killed by extended freeze-drying (EFD BCG) decreases lung and colon inflammation by recruiting IL-10-producing Tregs. Therefore, the aim of this study was to investigate the effect of EFD BCG on the development of atherosclerosis. DESIGN: We used two strains of atherosclerosis-prone mice: Ldlr(-/-) (four or six EFD BCG injections) and Apoe(-/-) (six injections). RESULTS: In both models, EFD BCG significantly reduced the size of atherosclerotic lesions, increased IL-10 production and reduced the serum levels of pro-inflammatory cytokines (IL-6, IL-13, KC and tumour necrosis factor-α). Shortly after treatment with EFD BCG, the number of plasmacytoid dendritic cells (pDCs) and Foxp3(+) Tregs in the draining lymph nodes increased. EFD BCG also led to accumulation of Tregs, but not of pDCs in the spleen, and reduced activity of NF-κB and increased activity of PPAR-γ in both the spleen and vascular tissue of treated mice. CONCLUSION: EFD BCG has atheroprotective effects through IL-10 production and Treg expansion. These findings support a novel approach to the prevention and treatment of atherosclerosis.

Inverse association between trans isomeric and long-chain polyunsaturated fatty acids in pregnant women and their newborns: data from three European countries.

BACKGROUND: trans unsaturated fatty acids are thought to interfere with essential fatty acid metabolism. To extend our knowledge of this phenomenon, we investigated the relationship between trans isomeric and long-chain polyunsaturated fatty acids (LCPUFA) in mothers during pregnancy and in their infants at birth. METHODS: Fatty acid composition of erythrocyte phosphatidylcholine (PC) and phosphatidylethanolamine (PE) was determined in Spanish (n = 120), German (n = 78) and Hungarian (n = 43) women at the 20th and 30th week of gestation, at delivery and in their newborns. RESULTS: At the 20th week of gestation, the sum of trans fatty acids in PE was significantly (p < 0.01) lower in Hungarian [0.73 (0.51), % wt/wt, median (IQR)] than in Spanish [1.42 (1.36)] and German [1.30 (1.21)] women. Docosahexaenoic acid (DHA) values in PE were significantly (p < 0.01) higher in Hungarian [5.65 (2.09)] than in Spanish [4.37 (2.60)] or German [4.39 (3.3.2)] women. The sum of trans fatty acids significantly inversely correlated to DHA in PCs in Spanish (r = -0.37, p < 0.001), German (n = -0.77, p < 0.001) and Hungarian (r = -0.35, p < 0.05) women, and in PEs in Spanish (r = -0.67, p < 0.001) and German (r = -0.71, p < 0.001), but not in Hungarian (r = -0.02) women. Significant inverse correlations were seen between trans fatty acids and DHA in PEs at the 30th week of gestation (n = 241, r = -0.52, p < 0.001), at delivery (n = 241, r = -0.40, p < 0.001) and in cord lipids (n = 218, r = -0.28, p < 0.001). CONCLUSION: Because humans cannot synthesize trans isomeric fatty acids, the data obtained in the present study support the concept that high maternal trans isomeric fatty acid intake may interfere with the availability of LCPUFA both for the mother and the fetus.

Spore traps network: a new tool for predicting epidemics of wheat yellow rust.

A network of Burkard 7-day spore-recording traps was set up in the Walloon Region in Belgium to monitor the airborne inoculum of wheat pathogens. The relationship between the airborne inoculum of Puccinia striiformis f.sp. tritici, the causal agent of stripe rust, and the disease incidence on plants in untreated plots located near each spore traps was studied during the 2008-2009 season. The presence of airborne inoculum was tested in four locations on tapes collected from the Burkard spore traps from 1 April to 14 June 2009. Total DNA from each fragment of spore trap tape corresponding to 1 day sampling was extracted. P. striiformis f.sp. tritici was quantified by real-time polymerase chain reaction (PCR) assay using specific primers and SYBRGreen. The airborne inoculum of P. striiformis was first detected between 7 and 13 April 2009, depending on the location in the Walloon Region. The first symptoms of stripe rust were observed in the fields between 15 May and 2 June 2009. The onset of the disease symptoms was always preceded by a higher peak of airborne inoculum about 15 days earlier. When P. striiformis f.sp. tritici was detected, the daily quantities of spores, collected from a volume of air of 14.4 m3, fluctuated between 0.23 and 154.66. This study shows that spore traps coupled with real-time PCR could be used to assess the airborne inoculum of P. striiformis in order to understand and predict stripe rust outbreaks.

Air embolism during liver procurement: an underestimated phenomenon? A pilot experimental study.

BACKGROUND: Intrahepatic air embolism can occur during liver transplantation, jeopardizing the posttransplant outcome. Until now, the role of the procurement in the origin of intrahepatic air remains unclear; it might be underestimated. In this pilot study using magnetic resonance imaging (MRI), we observed a substantial amount of air trapped in porcine livers during multiorgan procurement. We quantified the amount of air, examining whether it could be reduced by avoiding direct contact of air with the lumen of the hepatic vasculature during procurement and back-table preparation. METHODS: Five livers (control group) were procured according to standard techniques for comparison with 6 livers (modified group) where air could not enter into the livers due to clamping of the vasculature. MRI was performed during continuous machine perfusion (MP) preservation there after. We counted the number of black signal voids on T(2)*-weighted images, which were indicative of air bubbles within the hepatic contour. Additionally, an MRI contrast agent (gadolinium-diethylene triamine pentaacetic acid [Gd-DTPA]) was injected into the hepatic artery and circulated by MP. Insufficiently perfused areas with less contrast enhancement were analyzed quantitatively in T(1)-weighted images and expressed as the percentage of total liver volume. RESULTS: The images of the control livers showed more air bubbles compared with the modified group (45 ± 27 vs 6 ± 3; P = .004). The percentage of insufficiently perfused areas was higher among the control compared with the modified group (28.0 ± 15.8% vs 2.6 ± 4.6%; P = .047) on first-pass postcontrast T(1)-weighted images. After recirculating the contrast agent, insufficiently perfused areas showed similar localizations and contours within every liver. CONCLUSION: These data suggested that a substantial amount of air enters into the hepatic microcirculation through direct contact of air with the hepatic vasculature during standard procurement and back-table preparation. Avoiding opening the hepatic vessels to air substantially reduced this phenomenon.

Consistency of methods for analysing location-specific data.

Although the receiver operating characteristic (ROC) method is the acknowledged gold-standard for imaging system assessment, it ignores localisation information and differentiation between multiple abnormalities per case. As the free-response ROC (FROC) method uses localisation information and more closely resembles the clinical reporting process, it is being increasingly used. A number of methods have been proposed to analyse the data that result from an FROC study: jackknife alternative FROC (JAFROC) and a variant termed JAFROC1, initial detection and candidate analysis (IDCA) and ROC analysis via the reduction of the multiple ratings on a case to a single rating. The focus of this paper was to compare JAFROC1, IDCA and the ROC analysis methods using a clinical FROC human data set. All methods agreed on the ordering of the modalities and all yielded statistically significant differences of the figures-of-merit, i.e. p < 0.05. Both IDCA and JAFROC1 yielded much smaller p-values than ROC. The results are consistent with a recent simulation-based validation study comparing these and other methods. In conclusion, IDCA or JAFROC1 analysis of FROC human data may be superior at detecting modality differences than ROC analysis.

The relationship between the attenuation properties of breast microcalcifications and aluminum.

Screening mammography is one of the most challenging radiological techniques and this is partly due to the difficulty in detecting microcalcifications (MCs) against an anatomical background of varying mammographic tissue density. Further complicating factors in the detection of MCs include the small size and their resemblance to other bright structures in the breast. A number of different microcalcification simulating materials are available and these are often incorporated in test objects used to study some aspects of an imaging system, for example, optimal beam quality selection in digital mammography. Aluminum (Al) has similar x-ray attenuation properties to MCs and therefore Al is extensively used in test objects. However, to the best of our knowledge, the suitability of Al as a substitute material for MCs has not been studied explicitly. The aim of this study was therefore to demonstrate that spectral optimization studies for MCs can be performed with Al sheets. The approach used was twofold. First, contrasts generated by Al and MCs at several exposure settings were compared, and secondly an optimization study was performed with both Al and MCs as the contrasting target using an amorphous selenium (a-Se) based digital mammography unit. Specimens from stereotactic vacuum-assisted breast biopsies of non-palpable lesions with mammographic evidence of MCs were obtained from clinical routine patients. Contrasts generated by these MCs and by Al sheets were measured for Mo/Mo, Mo/Rh and W/Rh anode/filter combinations, for different polymethylmethacrylate (PMMA) thicknesses at the extremes of the x-ray tube voltages used clinically. A linear regression was then applied between the two measurements of contrast; the ratio of the angular coefficient q obtained from the fitted regression lines for Al and MCs ranged from 0.96 to 0.99 for Mo/Mo and Mo/Rh combinations at 2 and 4 cm PMMA, respectively, and from 0.83 at 4 cm PMMA to 1.14 at 7 cm PMMA for the W/Rh combination. For the optimization study, the signal-difference-to-noise ratio (SDNR) measured using the MCs was plotted as a function of mean glandular dose (MGD) for 4 cm PMMA, for the three different anode/filter combinations. The W/Rh combination always gave the highest SDNR for a given MGD. The SDNR and MGD were then used to define the common figure of merit SNR(2)/MGD; the setting that maximized this measure at 4 cm PMMA was 27 kV and a W/Rh combination. These results demonstrate a close correspondence between the attenuation properties of Al and extracted MC material over the energy range studied for the Mo/Mo, Mo/Rh and W/Rh anode/filter combinations. Furthermore, it was found that the exposure parameters that maximized the figure of merit for the MC specimen agree with results found in studies that used Al sheets as a substitute for the MC.

Distribution of airborne Mycosphaerella graminicola inoculum at the field scale.

A network of 10 Burkard 7-day spore-recording traps was set up in the Walloon region in Belgium to monitor the airborne inoculum of wheat pathogens. Three spore traps were used to analyse the distribution of Mycosphaerella graminicola inoculum at the field scale, at 1 m above ground level. Two traps were set up in a wheat field 100 m apart. The third trap was placed 70 m away in a sugar beet field adjacent to the wheat field. Total DNA from each fragment of spore trap tape corresponding to 1 day sampling was extracted and the quantity of M. graminicola was assessed using real-time polymerase chain reaction (PCR) assay. The experiment was conducted from July to October 2009. Positive detections were obtained for between 33 and 36 days, depending on the spore traps. When detected, the daily quantities of cDNA, collected from a volume of 14.4 m3, fluctuated between 4.84E+00 and 6.10E+03. Correlation coefficients higher than 0,82 and no significant differences were observed between the quantities of M. graminicola collected by the three spore traps, indicating that, at 1 m above ground level, the distribution of inoculum can be considered as homogenous at the tested field scale. This study confirms that spore traps coupled with real-time PCR could be used to assess the airborne inoculum of M. graminicola and to understand the development of the disease at this scale.

Dynamic contrast-enhanced and diffusion-weighted MRI for early detection of tumoral changes in single-dose and fractionated radiotherapy: evaluation in a rat rhabdomyosarcoma model.

We aimed to examine different intratumoral changes after single-dose and fractionated radiotherapy, using diffusion-weighted (DW) and dynamic contrast-enhanced (DCE) MRI in a rat rhabdomyosarcoma model. Four WAG/Rij rats with rhabdomyosarcomas in the flanks received single-dose radiotherapy of 8 Gy, and four others underwent fractionated radiotherapy (five times 3 Gy). In rats receiving single-dose radiotherapy, a significant perfusion decrease was found in the first 2 days post-treatment, with slow recuperation afterwards. No substantial diffusion changes could be seen; tumor growth delay was 12 days. The rats undergoing fractionated radiotherapy showed a similar perfusion decrease early after the treatment. However, a very strong increase in apparent diffusion coefficient occurred in the first 10 days; growth delay was 18 days. DW-MRI and DCE-MRI can be used to show early tumoral changes induced by radiotherapy. Single-dose and fractionated radiotherapy induce an immediate perfusion effect, while the latter induces more intratumoral necrosis.

Rat model of reperfused partial liver infarction: characterization with multiparametric magnetic resonance imaging, microangiography, and histomorphology.

BACKGROUND: Rat model of reperfused partial liver infarction (RPLI) has been increasingly used in studying new diagnostics and therapeutics. PURPOSE: To characterize the RPLI model using magnetic resonance imaging (MRI), microangiography, and histopathology. MATERIAL AND METHODS: RPLI was induced in eight rats by occluding hepatic inflow to the right liver lobe for 3 hours. MRI was performed at a 1.5 T clinical scanner 6 hours after reperfusion to obtain T2-weighted (T2WI), T1-weighted (T1WI), contrast-enhanced (CE) T1WI, diffusion-weighted imaging (DWI) with apparent diffusion coefficient (ADC) maps, T1-weighted dynamic contrast-enhanced (T1-DC) perfusion-weighted imaging (PWI), and T2*-weighted dynamic susceptibility contrast-enhanced (T2*-DSC) PWI images. Rats were sacrificed for microangiography and histomorphology. In vivo morphological and functional MRI parameters, including maximum initial slope (MIS), K value, relative blood flow (rBF), relative blood volume (rBV), time to peak (TTP), and mean transit time (MTT), were matched with postmortem findings. RESULTS: The infarcted lobe was conspicuous from normal liver with lower and higher signal intensity on T1WI (P=0.018) and T2WI (P=0.001), respectively. Contrast between infarcted and normal liver reversed on CE-T1WI after gadolinium injection. The infarction averaged 37.5% of total liver volume. DWI and ADC maps were able to detect subtle perfusion-related differences (P<0.05). With T1-DC-PWI, increased extravasation and vascular permeability were reflected by significantly greater MIS (P=0.034) and K value (P=0.014) in infarction. T2*-DSC-PWI showed lower rBF and rBV with shorter TTP and MTT in infarcted liver (P<0.05). In vivo MRI findings corresponded well with postmortem outcomes. CONCLUSION: RPLI in rats could be characterized by multiparametric MRI and postmortem assessments, with insight into the no-reflow phenomenon, which implies its further application for preclinical assessments of new pharmaceutics.

Comparison between effective radiation dose of CBCT and MSCT scanners for dentomaxillofacial applications.

OBJECTIVES: To compare the effective dose levels of cone beam computed tomography (CBCT) for maxillofacial applications with those of multi-slice computed tomography (MSCT). STUDY DESIGN: The effective doses of 3 CBCT scanners were estimated (Accuitomo 3D, i-CAT, and NewTom 3G) and compared to the dose levels for corresponding image acquisition protocols for 3 MSCT scanners (Somatom VolumeZoom 4, Somatom Sensation 16 and Mx8000 IDT). The effective dose was calculated using thermoluminescent dosimeters (TLDs), placed in a Rando Alderson phantom, and expressed according to the ICRP 103 (2007) guidelines (including a separate tissue weighting factor for the salivary glands, as opposed to former ICRP guidelines). RESULTS: Effective dose values ranged from 13 to 82 microSv for CBCT and from 474 to 1160 microSv for MSCT. CBCT dose levels were the lowest for the Accuitomo 3D, and highest for the i-CAT. CONCLUSIONS: Dose levels for CBCT imaging remained far below those of clinical MSCT protocols, even when a mandibular protocol was applied for the latter, resulting in a smaller field of view compared to various CBCT protocols. Considering this wide dose span, it is of outmost importance to justify the selection of each of the aforementioned techniques, and to optimise the radiation dose while achieving a sufficient image quality. When comparing these results to previous dosimetric studies, a conversion needs to be made using the latest ICRP recommendations.

Prenatal prediction of survival in isolated diaphragmatic hernia using observed to expected total fetal lung volume determined by magnetic resonance imaging based on either gestational age or fetal body volume.

OBJECTIVES: To compare the predictive value of the prenatal observed to expected (o/e) lung volume as measured by fetal magnetic resonance imaging (MRI), based on an algorithm using either the gestational age or fetal body volume (FBV), for neonatal survival of fetuses with isolated congenital diaphragmatic hernia (CDH). METHODS: We included 53 fetuses with a prenatal diagnosis of isolated CDH, 26 without and 27 with prenatal tracheal occlusion, who were assessed by fetal MRI, liveborn after 32 weeks, and in whom follow-up until discharge from the neonatal care unit was available. Measurements of lung volumes were expressed as a percentage of the appropriate mean (o/e total fetal lung volume (TFLV) x 100) either for gestational age or for FBV. Measurements of FBV were expressed as a percentage of the appropriate mean (o/e FBV x 100) for gestation. Fetuses with prenatal intervention were all assessed > or = 24 h after balloon removal. Regression analysis was used to examine the effect on postnatal survival of either o/e TFLV based on gestational age or based on FBV, gestation at delivery, side of CDH, intrathoracic position of the liver and prenatal intervention. Receiver-operating characteristics (ROC) curves were constructed for the prediction of survival by o/e TFLV based on gestational age and o/e TFLV based on FBV, for all fetuses, as well as for those with o/e FBV between 90 and 110% and those with values beyond that range. A power calculation for the number of fetuses needed to show a difference between the ROC curves was performed. RESULTS: Regression analysis demonstrated that o/e TFLV based on gestational age and on FBV were the only independent predictors of postnatal survival. The area under the ROC curve for prediction of postnatal survival from the o/e TFLV based on gestational age was 0.811, and for that based on FBV it was 0.868 (P < 0.001 for both). For fetuses with o/e FBV between 90 and 110%, and those with values < 90% and > 110%, the area for measurements based on gestational age was 0.895 and 0.733, respectively; when based on FBV it was 0.906 and 0.833 (P < 0.01 for all). A minimum of 273 patients would be needed to provide a probability of 90% of detecting a difference between the areas under both ROC curves. CONCLUSIONS: In fetuses with isolated CDH, lung volume as measured by fetal MRI was significantly correlated with survival. Prediction tended to be better by o/e TFLV based on FBV rather than gestational age. The difference in the prediction of survival between o/e TFLV based on FBV or gestational age was dependent on fetal biometry.

Relationship between fluorodeoxyglucose uptake in the large vessels and late aortic diameter in giant cell arteritis.

OBJECTIVE: GCA carries an increased risk of developing thoracic aortic aneurysms. Previous work with fluorodeoxyglucose (FDG)-PET has shown that the aorta is frequently involved in this type of vasculitis. We wanted to investigate whether there is a correlation between the extent of vascular FDG uptake during the acute phase of GCA and the aortic diameter at late follow-up. METHODS: All patients with biopsy-proven GCA who ever underwent an FDG-PET scan in our centre were asked to undergo a CT scan of the aorta. The diameter of the aorta was measured at six different levels (ascending aorta, aortic arch, descending aorta, abdominal suprarenal, juxtarenal and infrarenal aorta) and the volumes of the thoracic and of the abdominal aorta were calculated. RESULTS: Forty-six patients agreed to participate (32 females, 14 males). A mean of 46.7 +/- 29.9 months elapsed between diagnosis and CT scan. All aortic dimensions were significantly smaller in women than in men, except for the diameter of the ascending aorta. Patients who had an increased FDG uptake in the aorta at diagnosis of GCA, had a significantly larger diameter of the ascending aorta (P = 0.025) and descending aorta (P = 0.044) and a significantly larger volume of the thoracic aorta (P = 0.029). In multivariate analysis, FDG uptake at the thoracic aorta was associated with late volume of the thoracic aorta (P = 0.039). CONCLUSION: GCA-patients with increased FDG uptake in the aorta may be more prone to develop thoracic aortic dilatation than GCA patients without this sign of aortic involvement.

A quantitative method for evaluating the detectability of lesions in digital mammography.

This study presents a quantitative method for evaluating the detectability of microcalcifications in digital mammography. Four hundred and twenty microcalcifications (with various morphology, size and contrast), simulated with a previously validated method, were used for the creation of image datasets. Lesions were inserted into 163 regions of interests of 59 selected raw digital mammograms with various anatomical backgrounds and acquired with a Siemens Novation DR. After processing, these composite images were scored by experienced radiologists, who located multiple simulated lesions and rated them under conditions of free-search. For statistical analysis, free-response receiver-operating characteristic curves are plotted; the use of jackknife free-response receiver-operating characteristic method has also been investigated. The main advantage of this methodology is that the exact number of inserted microcalcifications is well known and that the lesions are fully characterised in terms of pathology, size, morphology and peak contrast. A first application has been the evaluation of the effect of anatomical background on microcalcifications detection. Preliminary findings in this study indicate that this method may be a promising tool to evaluate factors that have an influence on the detectability of lesions, such as the clinical processing or the viewing conditions.

Comparing two methods for assessment of perfusion-diffusion mismatch in a rodent model of ischaemic stroke: a pilot study.

This stroke experiment was designed to define the mismatch between perfusion-weighted imaging (PWI) and diffusion-weighted imaging (DWI) in MRI by applying early or instantly acquired PWI. Eight rats were induced with stroke through photothrombotic occlusion of the middle cerebral artery and scanned serially between 1 h and day 3 after induction using DWI and PWI with a 1.5 T MR scanner. The relative lesion volumes (rLV) on MRI and triphenyl tetrazolium chloride-stained specimens were defined as the proportion of lesion volume over brain volume. Discrepancies in the rLV between PWI- and DWI-derived apparent diffusion coefficient (ADC) maps were expressed by subtraction of the ADC from PWI, resulting in three possible patterns: (i) (PWI-ADC > 10% of PWI) denoting a mismatch; (ii) (-(10% of PWI)

Can apparent diffusion coefficient discriminate ischemic from nonischemic livers? A pilot experimental study.

PURPOSE: Using magnetic resonance imaging, the apparent diffusion coefficient (ADC) is an indicator to assess cerebral ischemia. The aim of this porcine study was to evaluate whether ADC assessed hepatic ischemia during ex vivo hypothermic machine perfusion (HMP) as well as in vivo. METHODS: Ex vivo: ADC of normal versus warm ischemic (WI) livers was assessed during HMP and subsequent rewarming to mimic ischemia-reperfusion injury. As the preservation solution, we used either an acellular solution or diluted blood. WI was induced in the left lobe or in the whole liver and compared 2-hour WI and non-WI. In vivo: One liver was scanned with the left lobe vessels occluded for 2-hour WI and subsequently for 3 hour reperfusion to compare with the right lobe without WI. Aspartate aminotransferase (AST) in the perfusate and morphology were used as surrogates of WI. RESULTS: In all WI livers, AST reached high levels and histology showed severe injury. Ex vivo ADC during acellular perfusion showed negligible differences between the livers with versus without WI, namely, 0.75 x 10(-3) or 0.88 x 10(-3) mm(2)/s during HMP. Ex vivo ADC using sanguineous perfusion showed 1.11 x 10(-3) or 0.83 x 10(-3) mm(2)/s during HMP in regions with versus without WI, respectively, a difference that remained stable during the whole experiment. ADC in vivo decreased from the physiological level of 1.07 x 10(-3) mm(2)/s to 0.75 x 10(-3) mm(2)/s in the first 30 minutes of WI, whereas ADC in the non-WI liver remained constant. CONCLUSION: ADC in vivo decreased during hepatic ischemia, as previously seen in cerebral ischemia. However, the effect of WI on ADC was less clear during ex vivo HMP.