Effect of vascular targeting agent in rat tumor model: dynamic contrast-enhanced versus diffusion-weighted MR imaging

PURPOSE: To compare dynamic contrast material-enhanced magnetic resonance (MR) imaging and diffusion-weighted MR imaging for noninvasive evaluation of early and late effects of a vascular targeting agent in a rat tumor model. MATERIALS AND METHODS: The study protocol was approved by the local ethics committee for animal care and use. Thirteen rats with one rhabdomyosarcoma in each flank (26 tumors) underwent dynamic contrast-enhanced imaging and diffusion-weighted echo-planar imaging in a 1.5-T MR unit before intraperitoneal injection of combretastatin A4 phosphate and at early (1 and 6 hours) and later (2 and 9 days) follow-up examinations after the injection. Histopathologic examination was performed at each time point. The apparent diffusion coefficient (ADC) of each tumor was calculated separately on the basis of diffusion-weighted images obtained with low b gradient values (ADC(low); b = 0, 50, and 100 sec/mm(2)) and high b gradient values (ADC(high); b = 500, 750, and 1000 sec/mm(2)). The difference between ADC(low) and ADC(high) was used as a surrogate measure of tissue perfusion (ADC(low) - ADC(high) = ADC(perf)). From the dynamic contrast-enhanced MR images, the volume transfer constant k and the initial slope of the contrast enhancement-time curve were calculated. For statistical analyses, a paired two-tailed Student t test and linear regression analysis were used. RESULTS: Early after administration of combretastatin, all perfusion-related parameters (k, initial slope, and ADC(perf)) decreased significantly (P < .001); at 9 days after combretastatin administration, they increased significantly (P < .001). Changes in ADC(perf) were correlated with changes in k (R(2) = 0.46, P < .001) and the initial slope (R(2) = 0.67, P < .001). CONCLUSION: Both dynamic contrast-enhanced MR imaging and diffusion-weighted MR imaging allow monitoring of perfusion changes induced by vascular targeting agents in tumors. Diffusion-weighted imaging provides additional information about intratumoral cell viability versus necrosis after administration of combretastatin.

Distribution of intramyocellular lipids in human calf muscles as determined by MR spectroscopic imaging

In this study the distribution of intramyocellular lipids (IMCL) in human calf muscles was determined by 1H-MR spectroscopic imaging (MRSI) measurements. An obstacle for MRSI measurements in the calf, including different muscles, is the inevitable inclusion of regions with high concentrations of extramyocellular lipids (EMCL). This can lead to signal bleeding and consequently to unpredictable overlaps of IMCL resonances with EMCL in voxels of interest. The results of this study show that signal bleeding from EMCL can be substantially reduced in voxels from calf muscles by the application of a lipid extrapolation (LE) procedure (Haupt et al., Magn Reson Med 1996;35:678). The spectra of all voxels located within muscle tissue were fitted, and the metabolite values were assigned to one of 10 different muscles based on image segmentation. Significant IMCL differences between some muscles were obtained, with high values in m. soleus and two to three times lower values in the tibialis anterior, tibialis posterior, and gastrocnemius muscles. In addition to gross differences between muscles, significant intersubject differences were observed in both IMCL content and distribution over different muscles. A significant correlation between fiber orientation (obtained from orientation-dependent dipolar coupling of creatine and taurine resonances) and IMCL content was found, indicating that IMCL content is directly correlated to biomechanical properties.

Linking brain connectivity across different time scales with electroencephalogram, functional magnetic resonance imaging, and diffusion tensor imaging

Structural and functional connectivity are intrinsic properties of the human brain and represent the amount of cognitive capacities of individual subjects. These connections are modulated due to development, learning, and disease. Momentary adaptations in functional connectivity alter the structural connections, which in turn affect the functional connectivity. Thus, structural and functional connectivity interact on a broad timescale. In this study, we aimed to explore distinct measures of connectivity assessed by functional magnetic resonance imaging and diffusion tensor imaging and their association to the dominant electroencephalogram oscillatory property at rest: the individual alpha frequency (IAF). We found that in 21 healthy young subjects, small intraindividual temporal IAF fluctuations were correlated to increased blood oxygenation level-dependent signal in brain areas associated to working memory functions and to the modulation of attention. These areas colocalized with functionally connected networks supporting the respective functions. Furthermore, subjects with higher IAF show increased fractional anisotropy values in fascicles connecting the above-mentioned areas and networks. Hence, due to a multimodal approach a consistent functionally and structurally connected network related to IAF was observed.

Integration of merged delayed-enhanced magnetic resonance imaging and multidetector computed tomography for the guidance of ventricular tachycardia ablation: a pilot study

BACKGROUND Delayed enhancement (DE) MRI can assess the fibrotic substrate of scar-related VT. MDCT has the advantage of inframillimetric spatial resolution and better 3D reconstructions. We sought to evaluate the feasibility and usefulness of integrating merged MDCT/MRI data in 3D-mapping systems for structure-function assessment and multimodal guidance of VT mapping and ablation. METHODS Nine patients, including 3 ischemic cardiomyopathy (ICM), 3 nonischemic cardiomyopathy (NICM), 2 myocarditis, and 1 redo procedure for idiopathic VT, underwent MRI and MDCT before VT ablation. Merged MRI/MDCT data were integrated in 3D-mapping systems and registered to high-density endocardial and epicardial maps. Low-voltage areas (<1.5 mV) and local abnormal ventricular activities (LAVA) during sinus rhythm were correlated to DE at MRI, and wall-thinning (WT) at MDCT. RESULTS Endocardium and epicardium were mapped with 391 ± 388 and 1098 ± 734 points per map, respectively. Registration of MDCT allowed visualization of coronary arteries during epicardial mapping/ablation. In the idiopathic patient, integration of MRI data identified previously ablated regions. In ICM patients, both DE at MRI and WT at MDCT matched areas of low voltage (overlap 94 ± 6% and 79 ± 5%, respectively). In NICM patients, wall-thinning areas matched areas of low voltage (overlap 63 ± 21%). In patients with myocarditis, subepicardial DE matched areas of epicardial low voltage (overlap 92 ± 12%). A total number of 266 LAVA sites were found in 7/9 patients. All LAVA sites were associated to structural substrate at imaging (90% inside, 100% within 18 mm). CONCLUSION The integration of merged MDCT and DEMRI data is feasible and allows combining substrate assessment with high-spatial resolution to better define structure-function relationship in scar-related VT.

Combined Ultrasmall Superparamagnetic Particles of Iron Oxide–Enhanced and Diffusion-weighted Magnetic Resonance Imaging Facilitates Detection of Metastases in Normal-sized Pelvic Lymph Nodes of Patients with Bladder and Prostate Cancer

Background Conventional cross-sectional imaging with computed tomography and magnetic resonance imaging (MRI) has limited accuracy for lymph node (LN) staging in bladder and prostate cancer patients. Objective To prospectively assess the diagnostic accuracy of combined ultrasmall superparamagnetic particles of iron oxide (USPIO) MRI and diffusion-weighted (DW) MRI in staging of normal-sized pelvic LNs in bladder and/or prostate cancer patients. Design, setting, and participants Examinations with 3-Tesla MRI 24–36 h after administration of USPIO using conventional MRI sequences combined with DW-MRI (USPIO-DW-MRI) were performed in 75 patients with clinically localised bladder and/or prostate cancer staged previously as N0 by conventional cross-sectional imaging. Combined USPIO-DW-MRI findings were analysed by three independent readers and correlated with histopathologic LN findings after extended pelvic LN dissection (PLND) and resection of primary tumours. Outcome measurements and statistical analysis Sensitivity and specificity for LN status of combined USPIO-DW-MRI versus histopathologic findings were evaluated per patient (primary end point) and per pelvic side (secondary end point). Time required for combined USPIO-DW-MRI reading was assessed. Results and limitations At histopathologic analysis, 2993 LNs (median: 39 LNs; range: 17–68 LNs per patient) with 54 LN metastases (1.8%) were found in 20 of 75 (27%) patients. Per-patient sensitivity and specificity for detection of LN metastases by the three readers ranged from 65% to 75% and 93% to 96%, respectively; sensitivity and specificity per pelvic side ranged from 58% to 67% and 94% to 97%, respectively. Median reading time for the combined USPIO-DW-MRI images was 9 min (range: 3–26 min). A potential limitation is the absence of a node-to-node correlation of combined USPIO-DW-MRI and histopathologic analysis. Conclusions Combined USPIO-DW-MRI improves detection of metastases in normal-sized pelvic LNs of bladder and/or prostate cancer patients in a short reading time.

Living Renal Allograft Transplantation: Diffusion-weighted MR Imaging in Longitudinal Follow-up of the Donated and the Remaining Kidney.

Purpose To determine whether diffusion-weighted (DW) magnetic resonance (MR) imaging in living renal allograft donation allows monitoring of potential changes in the nontransplanted remaining kidney of the donor because of unilateral nephrectomy and changes in the transplanted kidney before and after transplantation in donor and recipient, respectively, and whether DW MR parameters are correlated in the same kidney before and after transplantation. Materials and Methods The study protocol was approved by the local ethics committee; written informed consent was obtained. Thirteen healthy kidney donors and their corresponding recipients prospectively underwent DW MR imaging (multiple b values) in donors before donation and in donors and recipients at day 8 and months 3 and 12 after donation. Total apparent diffusion coefficient (ADCT) values were determined; contribution of microcirculation was quantified in perfusion fraction (FP). Longitudinal changes of diffusion parameters were compared (repeated-measures one-way analysis of variance with post hoc pairwise comparisons). Correlations were tested (linear regression). Results ADCT values in nontransplanted kidney of donors increased from a preexplantation value of (188 ± 9 [standard deviation]) to (202 ± 11) × 10(-5) mm(2)/sec in medulla and from (199 ± 11) to (210 ± 13) × 10(-5) mm(2)/sec in cortex 1 week after donation (P < .004). Medullary, but not cortical, ADCT values stayed increased up to 1 year. ADCT values in allografts in recipients were stable. Compared with values obtained before transplantation in donors, the corticomedullary difference was reduced in allografts (P < .03). Cortical ADCT values correlated with estimated glomerular filtration rate in recipients (R = 0.56, P < .001) but not donors. Cortical ADCT values in the same kidney before transplantation in donors correlated with those in recipients on day 8 after transplantation (R = 0.77, P = .006). FP did not show significant changes. Conclusion DW MR imaging depicts early adaptations in the remaining nontransplanted kidney of donors after nephrectomy. All diffusion parameters remained constant in allograft recipients after transplantation. This method has potential monitoring utility, although assessment of clinical relevance is needed. © RSNA, 2013 Online supplemental material is available for this article.

Approximate decoding approaches for network coded correlated data

This paper considers a framework where data from correlated sources are transmitted with the help of network coding in ad hoc network topologies. The correlated data are encoded independently at sensors and network coding is employed in the intermediate nodes in order to improve the data delivery performance. In such settings, we focus on the problem of reconstructing the sources at decoder when perfect decoding is not possible due to losses or bandwidth variations. We show that the source data similarity can be used at decoder to permit decoding based on a novel and simple approximate decoding scheme. We analyze the influence of the network coding parameters and in particular the size of finite coding fields on the decoding performance. We further determine the optimal field size that maximizes the expected decoding performance as a trade-off between information loss incurred by limiting the resolution of the source data and the error probability in the reconstructed data. Moreover, we show that the performance of the approximate decoding improves when the accuracy of the source model increases even with simple approximate decoding techniques. We provide illustrative examples showing how the proposed algorithm can be deployed in sensor networks and distributed imaging applications.

Post-Mortem Cardiac 3T Magnetic Resonance Imaging. Visualization of Sudden Cardiac Death?

OBJECTIVES: This study aimed to investigate post-mortem magnetic resonance imaging (pmMRI) for the assessment of myocardial infarction and hypointensities on post-mortem T2-weighted images as a possible method for visualizing the myocardial origin of arrhythmic sudden cardiac death. BACKGROUND: Sudden cardiac death has challenged clinical and forensic pathologists for decades because verification on post-mortem autopsy is not possible. pmMRI as an autopsy-supporting examination technique has been shown to visualize different stages of myocardial infarction. METHODS: In 136 human forensic corpses, a post-mortem cardiac MR examination was carried out prior to forensic autopsy. Short-axis and horizontal long-axis Images were acquired in situ on a 3-T system. RESULTS: In 76 cases, myocardial findings could be documented and correlated to the autopsy findings. Within these 76 study cases, a total of 124 myocardial lesions were detected on pmMRI (chronic: 25; subacute: 16; acute: 30; and peracute: 53). Chronic, subacute, and acute infarction cases correlated excellently to the myocardial findings on autopsy. Peracute infarctions (age range: minutes to approximately 1 h) were not visible on macroscopic autopsy or histological examination. Peracute infarction areas detected on pmMRI could be verified in targeted histological investigations in 62.3% of cases and could be related to a matching coronary finding in 84.9%. A total of 15.1% of peracute lesions on pmMRI lacked a matching coronary finding but presented with severe myocardial hypertrophy or cocaine intoxication facilitating a cardiac death without verifiable coronary stenosis. CONCLUSIONS: 3-T pmMRI visualizes chronic, subacute, and acute myocardial infarction in situ. In peracute infarction as a possible cause of sudden cardiac death, it demonstrates affected myocardial areas not visible on autopsy. pmMRI should be considered as a feasible post-mortem investigation technique for the deceased patient if no consent for a clinical autopsy is obtained.

Correlation between Accurate Electron Density and Linear Optical Properties in Amino Acid Derivatives: L-Histidinium Hydrogen Oxalate

The accurate electron density and linear optical properties of L-histidinium hydrogen oxalate are discussed. Two high-resolution single crystal X-ray diffraction experiments were performed and compared with density functional calculations in the solid state as well as in the gas phase. The crystal packing and the hydrogen bond network are accurately investigated using topological analysis based on quantum theory of atoms in molecules, Hirshfeld surface analysis, and electrostatic potential mapping. The refractive indices are computed from couple perturbed Kohn-Sham calculations and measured experimentally. Moreover, distributed atomic polarizabilities are used to analyze the origin of the linear susceptibility in the crystal, in order to separate molecular and intermolecular causes. The optical properties are also correlated with the electron density distribution. This compound also offers the possibility to test the electron density building block approach for material science and different refinement schemes for accurate positions and displacement parameters of hydrogen atoms, in the absence of neutron diffraction data.

Cardiovascular magnetization transfer ratio imaging compared with histology: A postmortem study

Cardiovascular magnetization transfer ratio (MTR) imaging by steady state free precession is a promising imaging method to assess microstructural changes within the myocardium. Hence, MTR imaging was correlated to histological analysis. Three postmortem cases were selected based on a suspicion of myocardial infarction. MTR and T2 -weighted (T2w ) imaging was performed, followed by autopsy and histological analysis. All tissue abnormalities, identified by autopsy or histology, were retrospectively selected on visually matched MTR and T2w images, and corresponding MTR values compared with normal appearing tissue. Regions of elevated MTR (up to approximately 20%, as compared to normal tissue), appearing hypo-intense in T2w -images, revealed the presence of fibrous tissue in microscopic histological analysis. Macroscopic observation (autopsy) described scar tissue only in one case. Regions of reduced MTR (up to approximately 20%) corresponded either to (i) the presence of edema, appearing hyperintense in T2w -images and confirmed by autopsy, or to (ii) inflammatory granulocyte infiltration at a microscopic level, appearing as hypo-intense T2w -signal, but not observed by autopsy. Findings from cardiovascular MTR imaging corresponded to histology results. In contrast to T2w -imaging, MTR imaging discriminated between normal myocardium, scar tissue and regions of acute myocardial infarction in all three cases. J. Magn. Reson. Imaging 2013. © 2013 Wiley Periodicals, Inc.

Implementing the plasma-lasing potential for tabletop nano-imaging

Implementing the plasma-lasing potential for tabletop nano-imaging on across a hot plasma medium drives short-wavelength lasing, promising for "turnkey" nano-imaging setups. A systematic study of the illumination characteristics, combined with design-adapted objectives, is presented. It is shown how the ultimate nano-scale feature is dictated by either the diffraction-limited or the wavefront-limited resolution, which imposed a combined study of both the source and the optics. For nano-imaging, the spatial homogeneity of the illumination (spot noise) was shown as critical. Plasma-lasing from a triple grazing-incidence pumping scheme compensated for the missing spot homogeneity in classical schemes. We demonstrate that a collimating mirror pre-conditions both the pointing stability and the divergence below half a mrad.

Estimation of heart weight by post-mortem cardiac magnetic resonance imaging

Introduction The aim of this study was to determine which single measurement on post-mortem cardiac MR reflects actual heart weight as measured at autopsy, assess the intra- and inter-observer reliability of MR measurements, derive a formula to predict heart weight from MR measurements and test the accuracy of the formula to prospectively predict heart weight. Materials and methods 53 human cadavers underwent post-mortem cardiac MR and forensic autopsy. In Phase 1, left ventricular area and wall thickness were measured on short axis and four chamber view images of 29 cases. All measurements were correlated to heart weight at autopsy using linear regression analysis. In Phase 2, single left ventricular area measurements on four chamber view images (LVA_4C) from 24 cases were used to predict heart weight at autopsy based on equations derived during Phase 1. Intra-class correlation coefficient (ICC) was used to determine inter- and intra-reader agreement. Results Heart weight strongly correlates with LVA_4C (r=0.78 M; p<0.001). Intra-reader and inter-reader reliability was excellent for LVA_4C (ICC=0.81–0.91; p<0.001 and ICC=0.90; p<0.001 respectively). A simplified formula for heart weight ([g]≈LVA_4C [mm2]×0.11) was derived based on linear regression analysis. Conclusions This study shows that single circumferential area measurements of the left ventricle in the four chamber view on post-mortem cardiac MR reflect actual heart weight as measured at autopsy. These measurements yield an excellent intra- and inter-reader reliability and can be used to predict heart weight prior to autopsy or to give a reasonable estimate of heart weight in cases where autopsy is not performed.

The value of susceptibility-weighted imaging (SWI) in patients with non-neonatal hypoxic-ischemic encephalopathy

OBJECTIVE In susceptibility-weighted imaging (SWI) in the normal brain, cortical veins appear hypointense due to paramagnetic properties of deoxy-hemoglobin. Global cerebral anoxia decreases cerebral oxygen metabolism, thereby increasing oxy-hemoglobin levels in cerebral veins. We hypothesized that a lower cerebral oxygen extraction fraction in comatose patients with non-neonatal hypoxic ischemic encephalopathy (IHE) produce a pattern of global rarefied or pseudo-diminished cortical veins due to higher oxy-hemoglobin. PURPOSE 1. To investigate the topographic relationship between susceptibility effects in cortical veins and related diffusion restrictions on diffusion-weighted imaging (DWI) in patients with IHE. 2. To relate imaging findings to patterns of altered resting activity on surface EEG. METHODS Twenty-three IHE patients underwent MRI. EEG patterns were used to classify the depth of coma. Regional vs. global susceptibility changes on SWI and patterns of DWI restrictions were compared with the depth of coma. RESULTS All patients exhibited areas of restricted cortical diffusion and SWI abnormalities. The dominant DWI restrictions encompassed widespread areas along the precuneus, frontal and parietal association cortices and basal ganglia. For SWI, nineteen patients had generalized bi-hemispherical patterns, the EEG patterns correlated with coma grades III to V. Four patients had focal decreases of deoxy-hemoglobin following DWI restrictions; associated with normal EEGs. CONCLUSION Focal patterns of diamagnetic effects on SWI according to relative decreases in deoxy-hemoglobin due to reduced metabolic demand are associated with normal EEG in IHE patients. Global patterns indicated increased depth of coma and widespread cortical damage. CLINICAL RELEVANCE The results indicate a potential diagnostic value of SWI in patients with IHE.

Relative indexes of cutaneous blood perfusion measured by real-time laser Doppler imaging (LDI) in healthy volunteers.

We used real-time LDI to study regional variations in microcirculatory perfusion in healthy candidates to establish a new methodology for global perfusion body mapping that is based on intra-individual perfusion index ratios. Our study included 74 (37 female) healthy volunteers aged between 22 and 30 years (mean 24.49). Imaging was performed using a recent microcirculation-imaging camera (EasyLDI) for different body regions of each volunteer. The perfusion values were reported in Arbitrary Perfusion Units (APU). The relative perfusion indexes for each candidate's body region were then obtained by normalization with the perfusion value of the forehead. Basic parameters such as weight, height, and blood pressure were also measured and analyzed. The highest mean perfusion value was reported in the forehead area (259.21APU). Mean perfusion in the measured parts of the body correlated positively with mean forehead value, while there was no significant correlation between forehead blood perfusion values and room temperature, BMI, systolic blood pressure and diastolic blood pressure (p=0.420, 0.623, 0.488, 0.099, respectively). Analysis of the data showed that perfusion indexes were not significantly different between male and female volunteers except for the ventral upper arm area (p=.001). LDI is a non-invasive, fast technique that opens several avenues for clinical applications. The mean perfusion indexes are useful in clinical practice for monitoring patients before and after surgical interventions. Perfusion values can be predicted for different body parts for patients only by taking the forehead perfusion value and using the perfusion index ratios to obtain expected normative perfusion values.

Comparison of gadoteric acid and gadobutrol for detection as well as morphologic and dynamic characterization of lesions on breast dynamic contrast-enhanced magnetic resonance imaging

OBJECTIVE In contrast to conventional breast imaging techniques, one major diagnostic benefit of breast magnetic resonance imaging (MRI) is the simultaneous acquisition of morphologic and dynamic enhancement characteristics, which are based on angiogenesis and therefore provide insights into tumor pathophysiology. The aim of this investigation was to intraindividually compare 2 macrocyclic MRI contrast agents, with low risk for nephrogenic systemic fibrosis, in the morphologic and dynamic characterization of histologically verified mass breast lesions, analyzed by blinded human evaluation and a fully automatic computer-assisted diagnosis (CAD) technique. MATERIALS AND METHODS Institutional review board approval and patient informed consent were obtained. In this prospective, single-center study, 45 women with 51 histopathologically verified (41 malignant, 10 benign) mass lesions underwent 2 identical examinations at 1.5 T (mean time interval, 2.1 days) with 0.1-mmol kg doses of gadoteric acid and gadobutrol. All magnetic resonance images were visually evaluated by 2 experienced, blinded breast radiologists in consensus and by an automatic CAD system, whereas the morphologic and dynamic characterization as well as the final human classification of lesions were performed based on the categories of the Breast imaging reporting and data system MRI atlas. Lesions were also classified by defining their probability of malignancy (morpho-dynamic index; 0%-100%) by the CAD system. Imaging results were correlated with histopathology as gold standard. RESULTS The CAD system coded 49 of 51 lesions with gadoteric acid and gadobutrol (detection rate, 96.1%); initial signal increase was significantly higher for gadobutrol than for gadoteric acid for all and the malignant coded lesions (P < 0.05). Gadoteric acid resulted in more postinitial washout curves and fewer continuous increases of all and the malignant lesions compared with gadobutrol (CAD hot spot regions, P < 0.05). Morphologically, the margins of the malignancies were different between the 2 agents, whereas gadobutrol demonstrated more spiculated and fewer smooth margins (P < 0.05). Lesion classifications by the human observers and by the morpho-dynamic index compared with the histopathologic results did not significantly differ between gadoteric acid and gadobutrol. CONCLUSIONS Macrocyclic contrast media can be reliably used for breast dynamic contrast-enhanced MRI. However, gadoteric acid and gadobutrol differed in some dynamic and morphologic characterization of histologically verified breast lesions in an intraindividual, comparison. Besides the standardization of technical parameters and imaging evaluation of breast MRI, the standardization of the applied contrast medium seems to be important to receive best comparable MRI interpretation.