Rapid functional reorganization of the forelimb cortical representation after thoracic spinal cord injury in adult rats.

Thoracic spinal cord injured rats rely largely on forelimbs to walk, as their hindlimbs are dysfunctional. This increased limb use is accompanied by expansion of the cortical forelimb sensory representation. It is unclear how quickly the representational changes occur and whether they are at all related to the behavioral adaptation. Using blood oxygenation level dependent functional mangetic resonance imaging (BOLD-fMRI) we show that major plastic changes of the somato-sensory map can occur as early as one day after injury. The extent of map increase was variable between animals, and some animals showed a reduction in map size. However, at three or seven days after injury a significant enhancement of the forelimb representation was evident in all the animals. In a behavioral test for precise limb control, crossing of a horizontal ladder, the injured rats relied almost entirely on their forelimbs; they initially made more mistakes than at 7 days post injury. Remarkably, in the individual animals the behavioral performance seen at seven days was proportional to the physiological change present at one day after injury. The rapid increase in cortical representation of the injury-spared body part may provide the additional neural substrate necessary for high level behavioral adaptation.

Contrast-enhanced magnetic resonance microangiography reveals remodeling of the cerebral microvasculature in transgenic ArcAß mice.

Amyloid-ß (Aß) deposition in the cerebral vasculature is accompanied by remodeling which has a profound influence on vascular integrity and function. In the current study we have quantitatively assessed the age-dependent changes of the cortical vasculature in the arcAß model of cerebral amyloidosis. To estimate the density of the cortical microvasculature in vivo, we used contrast-enhanced magnetic resonance microangiography (CE-µMRA). Three-dimensional gradient echo datasets with 60 µm isotropic resolution were acquired in 4- and 24-month-old arcAß mice and compared with wild-type (wt) control mice of the same age before and after administration of superparamagnetic iron oxide nanoparticles. After segmentation of the cortical vasculature from difference images, an automated algorithm was applied for assessing the number and size distribution of intracortical vessels. With CE-µMRA, cerebral arteries and veins with a diameter of less than the nominal pixel resolution (60 µm) can be visualized. A significant age-dependent reduction in the number of functional intracortical microvessels (radii of 20-80 µm) has been observed in 24-month-old arcAß mice compared with age-matched wt mice, whereas there was no difference between transgenic and wt mice of 4 months of age. Immunohistochemistry demonstrated strong fibrinogen and Aß deposition in small- and medium-sized vessels, but not in large cerebral arteries, of 24-month-old arcAß mice. The reduced density of transcortical vessels may thus be attributed to impaired perfusion and vascular occlusion caused by deposition of Aß and fibrin. The study demonstrated that remodeling of the cerebrovasculature can be monitored noninvasively with CE-µMRA in mice.

Loss of angiomiR-126 and 130a in angiogenic early outgrowth cells from patients with chronic heart failure: role for impaired in vivo neovascularization and cardiac repair capacity.

BACKGROUND: MicroRNAs are key regulators of angiogenic processes. Administration of angiogenic early outgrowth cells (EOCs) or CD34(+) cells has been suggested to improve cardiac function after ischemic injury, in particular by promoting neovascularization. The present study therefore examines regulation of angiomiRs, microRNAs involved in angiogenesis, in angiogenic EOCs and circulating CD34(+) cells from patients with chronic heart failure (CHF) and the role for their cardiac repair capacity. METHODS AND RESULTS: Angiogenic EOCs and CD34(+) cells were isolated from patients with CHF caused by ischemic cardiomyopathy (n=45) and healthy subjects (n=35). In flow cytometry analyses, angiogenic EOCs were largely myeloid and positive for alternatively activated M2 macrophage markers. In vivo cardiac neovascularization and functional repair capacity were examined after transplantation into nude mice with myocardial infarction. Cardiac transplantation of angiogenic EOCs from healthy subjects markedly increased neovascularization and improved cardiac function, whereas no such effect was observed after transplantation of angiogenic EOCs from patients with CHF. Real-time polymerase chain reaction analysis of 14 candidate angiomiRs, expressed in angiogenic EOCs, revealed a pronounced loss of angiomiR-126 and -130a in angiogenic EOCs from patients with CHF that was also observed in circulating CD34(+) cells. Anti-miR-126 transfection markedly impaired the capacity of angiogenic EOCs from healthy subjects to improve cardiac function. miR-126 mimic transfection increased the capacity of angiogenic EOCs from patients with CHF to improve cardiac neovascularization and function. CONCLUSIONS: The present study reveals a loss of angiomiR-126 and -130a in angiogenic EOCs and circulating CD34(+) cells from patients with CHF. Reduced miR-126 expression was identified as a novel mechanism limiting their capacity to improve cardiac neovascularization and function that can be targeted by miR-126 mimic transfection.

Functional MRI to assess alterations of functional networks in response to pharmacological or genetic manipulations of the serotonergic system in mice.

Imaging methods that enable the investigation of functional networks both in human and animal brain provide important insights into mechanisms underlying pathologies including psychiatric disorders. Since the serotonergic receptor 1A (5-HT(1A)-R) has been strongly implicated in the pathophysiology of depressive and anxiety disorders, as well as in the action of antidepressant drugs, we investigated brain connectivity related to the 5-HT(1A)-R system by use of pharmacological functional magnetic resonance imaging in mice. We characterized functional connectivity elicited by activation of 5-HT(1A)-R and investigated how pharmacological and genetic manipulations of its function may modulate the evoked connectivity. Functional connectivity elicited by administration of the 5-HT(1A)-R agonist 8-OH-DPAT can be described by networks characterized by small-world attributes with nodes displaying highly concerted response patterns. Circuits identified comprised the brain structures known to be involved in stress-related disorders (e.g. prefrontal cortex, amygdala and hippocampus). The results also highlight the dorsomedial thalamus, a structure associated with fear processing, as a hub of the 5-HT(1A)-R functional network. Administration of a specific 5-HT(1A)-R antagonist or use of heterozygous 5-HT(1A)-R knockout mice significantly reduced functional connectivity elicited by 8-OH-DPAT. Whole brain functional connectivity analysis constitutes an attractive tool to characterize impairments in neurotransmission and the efficacy of pharmacological treatment in a comprehensive manner.

Optimized Varian aSi portal dosimetry: development of datasets for collective use.

Although much literature has been devoted to portal dosimetry with the Varian amorphous silicon (aSi) portal imager, the majority of the described methods are not routinely adopted because implementation procedures are cumbersome and not within easy reach of most radiotherapy centers. To make improved portal dosimetry solutions more generally available, we have investigated the possibility of converting optimized configurations into ready-to-use standardized datasets. Firstly, for all commonly used photon energies (6, 10, 15, 18, and 20 MV), basic beam data acquired on 20 aSi panels were used to assess the interpanel reproducibility. Secondly, a standardized portal dose image prediction (PDIP) algorithm configuration was created for every energy, using a three-step process to optimize the aSi dose response function and profile correction files for the dosimetric calibration of the imager panel. An approximate correction of the backscatter of the Exact arm was also incorporated. Thirdly, a set of validation fields was assembled to assess the accuracy of the standardized configuration. Variations in the basic beam data measured on different aSi panels very rarely exceeded 2% (2 mm) and are of the same order of magnitude as variations between different Clinacs when measuring in reference conditions in water. All studied aSi panels can hence be regarded as nearly identical. Standardized datasets were successfully created and implemented. The test package proved useful in highlighting possible problems and illustrating remaining limitations, but also in demonstrating the good overall results (95% pass rate for 3%,3 mm) that can be obtained. The dosimetric behavior of all tested aSi panels was found to be nearly identical for all tested energies. The approach of using standardized datasets was then successfully tested through the creation and evaluation of PDIP preconfigured datasets that can be used within the Varian portal dosimetry solution.

MRI signature in a novel mouse model of genetically induced adult oligodendrocyte cell death.

Two general pathological processes contribute to multiple sclerosis (MS): acute inflammation and degeneration. While magnetic resonance imaging (MRI) is highly sensitive in detecting abnormalities related to acute inflammation both clinically and in animal models of experimental autoimmune encephalomyelitis (EAE), the correlation of these readouts with acute and future disabilities has been found rather weak. This illustrates the need for imaging techniques addressing neurodegenerative processes associated with MS. In the present work we evaluated the sensitivity of different MRI techniques (T(2) mapping, macrophage tracking based on labeling cells in vivo by ultrasmall particles of iron oxide (USPIO), diffusion tensor imaging (DTI) and magnetization transfer imaging (MTI)) to detect histopathological changes in a novel animal model making use of intrinsic, temporally and spatially controlled triggering of oligodendrocyte cell death. This mouse model allows studying the MRI signature associated to neurodegenerative processes of MS in the absence of adaptive inflammatory components that appear to be foremost in the EAE models. Our results revealed pronounced T(2) hyperintensities in brain stem and cerebellar structures, which we attribute to structural alteration of white matter by pronounced vacuolation. Brain areas were found devoid of significant macrophage infiltration in line with the absence of a peripheral inflammatory response. The significant decrease in diffusion anisotropy derived from DTI measures in these structures is mainly caused by a pronounced decrease in diffusivity parallel to the fiber indicative of axonal damage. Triggering of oligodendrocyte ablation did not translate into a significant increase in radial diffusivity. Only minor decreases in MT ratio have been observed, which is attributed to inefficient removal of myelin debris.

Increased blood oxygen level-dependent (BOLD) sensitivity in the mouse somatosensory cortex during electrical forepaw stimulation using a cryogenic radiofrequency probe.

Functional MRI (fMRI) based on the blood oxygen level-dependent (BOLD) contrast is widely used in preclinical neuroscience. The small dimensions of rodent brain place high demands on spatial resolution, and hence on the sensitivity of the fMRI experiment. This work investigates the performance of a 400-MHz cryogenic quadrature transceive radiofrequency probe (CryoProbe) with respect to the enhancement of the BOLD sensitivity. For this purpose, BOLD fMRI experiments were performed in mice during electrical forepaw stimulation using the CryoProbe and a conventional room temperature surface coil of comparable dimensions. Image signal-to-noise ratio (SNR) and temporal SNR were evaluated as quality measures for individual images and for fMRI time series of images, resulting in gains (mean ± standard deviation) with factors of 3.1 ± 0.7 and 1.8 ± 1.0 when comparing the CryoProbe and room temperature coil. The CryoProbe thermal shield temperature did not affect the noise characteristics, with temporal noise levels being 63 ± 16% of the corresponding room temperature value. However, a significant effect on BOLD amplitudes was found, which was attributed to temperature-dependent baseline cerebral blood volumes. Defined local thermal conditions were found to be a critical parameter for achieving an optimal and reproducible fMRI signal. In summary, the CryoProbe represents an attractive alternative for the enhancement of image SNR, temporal SNR and BOLD sensitivity in mouse fMRI experiments.

Longitudinal evaluation of intramyocellular lipids (IMCLs) in tibialis anterior muscle of ob/ob and ob/+ control mice using a cryogenic surface coil at 9.4 T.

Insulin resistance is a central feature of type II diabetes and is associated with alterations in skeletal muscle lipid metabolism, which manifest themselves, in part, in increased intramyocellular lipid (IMCL) accumulation. The objective of this study was to assess noninvasively the levels of IMCL longitudinally in the tibialis anterior muscle of Lep(ob) /Lep(ob) (ob/ob) mice, a genetic model of obesity and mild diabetes, and Lep(ob) /+ (ob/+) heterozygous control animals, using (1) H MRS at 9.4 T. The use of a cryogenic surface coil transceiver leads to significant increases in sensitivity. Method implementation included the assessment of the reproducibility and spatial heterogeneity of the IMCL signal and the determination of T(2) relaxation times, as IMCL levels were expressed relative to the total creatine signal, and therefore the signal ratios had to be corrected for differences in T(2) relaxation. IMCL levels were found to be significantly higher in ob/ob mice relative to ob/+ heterozygous control mice that do not develop disease. An increase in IMCL levels was observed for ob/ob mice until weeks 16/17; after this time point, IMCL levels decreased again, reaching final levels that were slightly higher than the initial values. These noninvasively detected alterations in skeletal muscle lipid metabolism in ob/ob mice were accompanied by a transient increase in plasma insulin concentrations. This study indicates that IMCL may be reliably assessed in mouse tibialis anterior muscle using a cryogenic surface coil, implying that (1) H MRS at 9.4 T represents a useful technology for the noninvasive measurement of changes in lipid metabolism in the skeletal muscle that accompany obesity.

Analytic image concept combined to SENSE reconstruction.

OBJECT: Two approaches of reconstructing undersampled partial k-space data, acquired with multiple coils are compared: homodyne detection combined with SENSE (HM_SENSE) and analytic image reconstruction combined with SENSE (AI_SENSE). The latter overcomes limitations of HM_ SENSE by considering aliased images as analytic thus avoiding the need for phase correction required for HM_SENSE. MATERIALS AND METHODS: In vivo imaging experiments were carried out in male Lewis rats using both gradient echo and spin echo sequences. Accelerated images obtained by using the various reconstruction algorithms were compared to fully sampled reference images both qualitatively and quantitatively. RESULTS: For the various sampling patterns evaluated, both HM_SENSE and AI_SENSE were found to yield robust image reconstruction with small deviations from the reference image. Even for high acceleration factors AI_SENSE still provided useful results and was found superior compared to HM_SENSE. CONCLUSION: Combination of partial k-space sampling and parallel image acquisition allows for further acceleration of data acquisition as compared to each method alone. Image reconstruction from undersampled data sets using the AI_SENSE algorithm was found to considerably reduce reconstruction errors and artifacts observed for HM_SENSE reconstruction caused by errors in phase estimation.

Accurate assessment of carotid artery stenosis in atherosclerotic mice using accelerated high-resolution 3D magnetic resonance angiography.

OBJECT: High-resolution magnetic resonance angiography (MRA) enables non-invasive detection and longitudinal monitoring of atherosclerosis in mouse models of human disease. However, MRA is hampered by long acquisition times putting high demands on the physiological stability of the animal. Therefore, we evaluated the feasibility of accelerated MRA using the parallel imaging technique SENSE with regard to both lesion detection and quantification. MATERIALS AND METHODS: MRA acquisitions of supra-aortic vessels were performed in ApoE (-/-) mice that have been shown to develop atherosclerotic plaques. Findings obtained from accelerated data sets were compared to fully sampled reference data sets and histology. RESULTS: Our results revealed only minor differences in detecting vascular lesions for data collections accelerated by factors of up to 3.3 using a four-element coil array. For vessels with a mean lumen diameter of 500 µm, morphometry of stenotic lesions revealed no substantial deviations from reference (fully sampled) data for all investigated acceleration factors. For the highest acceleration factor of 3.3, an average deviation of the degree of stenosis of 4.9 ± 3.6% was found. Common carotid stenoses assessed by in vivo MRA displayed a good correlation with histological analyses (slope of linear regression = 0.97, R (2) = 0.98). CONCLUSION: According to the results of this work, we have demonstrated the feasibility and accuracy of accelerated high-resolution 3D ToF MRA in mice suitable for detailed depiction of mouse supra-aortic vessels and amenable to non-invasive quantification of small atherosclerotic lesions.

Functional and anatomical reorganization of the sensory-motor cortex after incomplete spinal cord injury in adult rats.

A lateral hemisection injury of the cervical spinal cord results in Brown-Séquard syndrome in humans and rats. The hands/forelimbs on the injured side are rendered permanently impaired, but the legs/hindlimbs recover locomotor functions. This is accompanied by increased use of the forelimb on the uninjured side. Nothing is known about the cortical circuits that correspond to these behavioral adaptations. In this study, on adult rats with cervical spinal cord lateral hemisection lesions (at segment C3/4), we explored the sensory representation and corticospinal projection of the intact (ipsilesional) cortex. Using blood oxygenation level-dependent functional magnetic resonance imaging and voltage-sensitive dye (VSD) imaging, we found that the cortex develops an enhanced representation of the unimpaired forepaw by 12 weeks after injury. VSD imaging also revealed the cortical spatio-temporal dynamics in response to electrical stimulation of the ipsilateral forepaw or hindpaw. Interestingly, stimulation of the ipsilesional hindpaw at 12 weeks showed a distinct activation of the hindlimb area in the intact, ipsilateral cortex, probably via the injury-spared spinothalamic pathway. Anterograde tracing of corticospinal axons from the intact cortex showed sprouting to recross the midline, innervating the spinal segments below the injury in both cervical and lumbar segments. Retrograde tracing of these midline-crossing axons from the cervical spinal cord (at segment C6/7) revealed the formation of a new ipsilateral forelimb representation in the cortex. Our results demonstrate profound reorganizations of the intact sensory-motor cortex after unilateral spinal cord injury. These changes may contribute to the behavioral adaptations, notably for the recovery of the ipsilesional hindlimb.

Accelerated cardiovascular magnetic resonance of the mouse heart using self-gated parallel imaging strategies does not compromise accuracy of structural and functional measures.

BACKGROUND: Self-gated dynamic cardiovascular magnetic resonance (CMR) enables non-invasive visualization of the heart and accurate assessment of cardiac function in mouse models of human disease. However, self-gated CMR requires the acquisition of large datasets to ensure accurate and artifact-free reconstruction of cardiac cines and is therefore hampered by long acquisition times putting high demands on the physiological stability of the animal. For this reason, we evaluated the feasibility of accelerating the data collection using the parallel imaging technique SENSE with respect to both anatomical definition and cardiac function quantification. RESULTS: Findings obtained from accelerated data sets were compared to fully sampled reference data. Our results revealed only minor differences in image quality of short- and long-axis cardiac cines: small anatomical structures (papillary muscles and the aortic valve) and left-ventricular (LV) remodeling after myocardial infarction (MI) were accurately detected even for 3-fold accelerated data acquisition using a four-element phased array coil. Quantitative analysis of LV cardiac function (end-diastolic volume (EDV), end-systolic volume (ESV), stroke volume (SV), ejection fraction (EF) and LV mass) in healthy and infarcted animals revealed no substantial deviations from reference (fully sampled) data for all investigated acceleration factors with deviations ranging from 2% to 6% in healthy animals and from 2% to 8% in infarcted mice for the highest acceleration factor of 3.0. CNR calculations performed between LV myocardial wall and LV cavity revealed a maximum CNR decrease of 50% for the 3-fold accelerated data acquisition when compared to the fully-sampled acquisition. CONCLUSIONS: We have demonstrated the feasibility of accelerated self-gated retrospective CMR in mice using the parallel imaging technique SENSE. The proposed method led to considerably reduced acquisition times, while preserving high spatial resolution at sufficiently high CNR. The accuracy of measurements of both structural and functional parameters of the mouse heart was not compromised by the application of the proposed accelerated data acquisition method.

Increasing temporal resolution of DSC perfusion MRI using the analytic image concept.

OBJECT: Dynamic susceptibility contrast MRI (DSC-MRI) is increasingly being used to evaluate cerebral microcirculation. In this study, the use of the analytic image reconstruction (AIR), with the aim to increase the temporal resolution, is evaluated for DSC-MRI in small animals. MATERIALS AND METHODS: Imaging was performed using a T (2)*- weighted sequence to acquire male Lewis rats raw data. Results show that AIR satisfactory reconstructs DSC-MRI while preserving a good reconstruction quality and the image characteristics compared to the full k-space and keyhole reconstructed images. The combination of the choice of the baseline image and the proposed asymmetric acquisition schema enables an increase in temporal resolution, by a factor of four, thus having more sample points for better estimating perfusion parameters. RESULTS: Computer simulations result in a mean cerebral blood volume of 1.22 that deviates from the full k-space value by -3% and a mean cerebral blood flow of 1.97 deviating from the full k-space value by -3% when the mean transit time did not change. Even if these deviations increase when achieving real acquisitions, AIR still better computes quantitative values than keyhole. CONCLUSION: AIR allows a good reconstruction of the dynamic stage of the image series thus leading to better dynamic effects analysis.

Functional reorganization in rat somatosensory cortex assessed by fMRI: elastic image registration based on structural landmarks in fMRI images and application to spinal cord injured rats.

The accuracy at which changes in cortical functional topology can be assessed by functional MRI (fMRI) depends on the quality of the reference coordinate system used for comparison of data sets obtained in different imaging sessions. Current procedures comprise an overlay of activation clusters on registered high-resolution anatomical images. Yet, fMRI images are frequently distorted due to susceptibility artifacts, which are prominent in rodent studies due to the small dimensions involved and high magnetic field strengths used. Therefore, a procedure for co-registration of activation maps has been developed based on anatomical landmarks defined on fMR echo planar images (EPI) themselves. Validation studies in control rats revealed that the centers of activated areas in somatosensory cortex S1, evoked through sensory forepaw stimulation fell within an area of 1 x 1 mm(2) in agreement with known electrophysiological coordinates. The technique was applied to detect changes in activation patterns in rats following smaller unilateral spinal cord injuries (SCI) in their cervical segments (C3/C4) 12 weeks after lesion. Despite of an almost complete behavioral recovery, fMRI responses remained altered in SCI animals with both significantly reduced fMRI signal amplitude and reduced latency to reach the peak response. Moreover, in SCI animals the activated S1 area corresponding to the contralesional forepaw was significantly enlarged and the center-of-mass for the ipsilesional paw was shifted rostrally. The mapping technique described combined with the temporal analysis of the BOLD response enabled a noninvasive quantitative characterization of cortical functional reorganization following SCI in rats.

Molecular neuroimaging in rodents: assessing receptor expression and function.

Multimodal non-invasive neuroimaging in rodents constitutes an attractive tool for studying neurobiological processes in vivo. At present, imaging studies of brain anatomy and function as well as the investigation of structure-function relationships belong to the standard repertoire of neuroscientists. Molecular imaging adds a new perspective. The mapping of the receptor distribution and receptor occupancy can nowadays be complemented by specific readouts of receptor function either by visualizing the activity of signaling pathways or mapping the physiological consequences of receptor stimulation. Molecular information is obtained through the use of imaging probes that combine a target-specific ligand with a reporter moiety that generates a signal that can be detected from outside the body. For imaging probes targeting the central nervous system, penetration of the intact blood-brain barrier constitutes a major hurdle. Molecular imaging generates specific information and therefore has a large potential for disease phenotyping (diagnostics), therapy development and monitoring of treatment response. Molecular imaging is still in its infancy and major developments in imaging technology, probe design and data analysis are required in order to make an impact. Rodent molecular neuroimaging will play an important role in the development of these tools.

Micro MRI of the mouse brain using a novel 400 MHz cryogenic quadrature RF probe.

The increasing number of mouse models of human disease used in biomedical research applications has led to an enhanced interest in non-invasive imaging of mice, e.g. using MRI for phenotyping. However, MRI of small rodents puts high demands on the sensitivity of data acquisition. This requirement can be addressed by using cryogenic radio-frequency (RF) detection devices. The aim of this work was to investigate the in vivo performance of a 400 MHz cryogenic transmit/receive RF probe (CryoProbe) designed for MRI of the mouse brain. To characterize this novel probe, MR data sets were acquired with both the CryoProbe and a matched conventional receive-only surface coil operating at room temperature (RT) using conventional acquisition protocols (gradient and spin echo) with identical parameter settings. Quantitative comparisons in phantom and in vivo experiments revealed gains in the signal-to-noise ratio (SNR) of 2.4 and 2.5, respectively. The increased sensitivity of the CryoProbe was invested to enhance the image quality of high resolution structural images acquired in scan times compatible with routine operation (< 45 min). In high resolution (30 x 30 x 300 microm(3)) structural images of the mouse cerebellum, anatomical details such as Purkinje cell and molecular layers could be identified. Similarly, isotropic (60 x 60 x 60 microm(3)) imaging of mouse cortical and subcortical areas revealed anatomical structures smaller than 100 microm. Finally, 3D MR angiography (52 x 80 x 80 microm(3)) of the brain vasculature enabled the detailed reconstruction of intracranial vessels (anterior and middle cerebral artery). In conclusion, this low temperature detection device represents an attractive option to increase the performance of small animal MR systems operating at 9.4 Tesla.

Frequency domain measurements on turbid media with strong absorption using the PN approximation.

We have applied the frequency-domain technique to measurement of the optical properties of turbid media with strong absorption in the infinite medium limit. Absorption coefficients up to 2.3 cm(-1) for a modified scattering coefficient of 4.3 cm(-1) are studied, which corresponds to a reduced scattering albedo of 0.65. Low phase noise and good phase stability are required for these low albedo conditions. As the degree of absorption increases, the phase changes are reduced while amplitude changes increase. For this reason, correction of amplitude-phase cross talk is essential to achieve accurate measurements with strong absorption. Careful control of stray reflections is required to properly measure amplitude-phase cross talk. Because the diffusion approximation becomes less accurate, measurements are compared to calculations performed in the PN approximation, which is essentially an exact solution for the infinite medium limit. Agreement between theory and experiment is only obtained when correction for amplitude-phase cross talk is performed. These measurements can provide a good method for testing amplitude-phase cross talk.

Determination of peak velocity in stenotic areas: echocardiography versus k-t SENSE accelerated MR Fourier velocity encoding.

The study was approved by the local ethical committees, and informed consent from each participant was obtained. The purpose of the study was to compare accelerated magnetic resonance (MR) Fourier velocity encoding (FVE), MR phase-contrast velocity mapping, and echocardiography with respect to peak velocity determination in vascular or valvular stenoses. FVE data collection was accelerated by using the k-space and time sensitivity encoding, or k-t SENSE, technique. Peak velocities were evaluated in five healthy volunteers (one woman, four men; mean age, 28 years; range, 23-34 years), three patients with stenotic aortic valves (two women, one man; mean age, 67 years; range, 39-82 years), two patients with pulmonary valvular stenosis (a 14-year-old girl and a 36-year-old man), and two patients with aortic stenosis (two women aged 18 and 27 years). In volunteers, peak velocity determined by the different methods agreed well. In patients, similar peak velocities were obtained by using accelerated MR FVE and echocardiography, while phase-contrast MR imaging results tended to underestimate these values.

Detection of anatomical changes in lung cancer patients with 2D time-integrated, 2D time-resolved and 3D time-integrated portal dosimetry: a simulation study.

The aim of this work is to assess the performance of 2D time-integrated (2D-TI), 2D time-resolved (2D-TR) and 3D time-integrated (3D-TI) portal dosimetry in detecting dose discrepancies between the planned and (simulated) delivered dose caused by simulated changes in the anatomy of lung cancer patients. For six lung cancer patients, tumor shift, tumor regression and pleural effusion are simulated by modifying their CT images. Based on the modified CT images, time-integrated (TI) and time-resolved (TR) portal dose images (PDIs) are simulated and 3D-TI doses are calculated. The modified and original PDIs and 3D doses are compared by a gamma analysis with various gamma criteria. Furthermore, the difference in the D 95% (ΔD 95%) of the GTV is calculated and used as a gold standard. The correlation between the gamma fail rate and the ΔD 95% is investigated, as well the sensitivity and specificity of all combinations of portal dosimetry method, gamma criteria and gamma fail rate threshold. On the individual patient level, there is a correlation between the gamma fail rate and the ΔD 95%, which cannot be found at the group level. The sensitivity and specificity analysis showed that there is not one combination of portal dosimetry method, gamma criteria and gamma fail rate threshold that can detect all simulated anatomical changes. This work shows that it will be more beneficial to relate portal dosimetry and DVH analysis on the patient level, rather than trying to quantify a relationship for a group of patients. With regards to optimizing sensitivity and specificity, different combinations of portal dosimetry method, gamma criteria and gamma fail rate should be used to optimally detect certain types of anatomical changes.

Evaluation of the Machine Performance Check application for TrueBeam Linac.

BACKGROUND: Machine Performance Check (MPC) is an application to verify geometry and beam performances of TrueBeam Linacs, through automated checks based on their kV-MV imaging systems. In this study, preliminary tests with MPC were analyzed using all photon beam energies of our TrueBeam, comparing whenever possible with external independent checks. METHODS: Data acquisition comprises a series of 39 images (12 with kV and 27 with MV detector) acquired at predefined positions without and with the IsoCal phantom in the beam, and with particular MLC pattern settings. MPC performs geometric and dosimetric checks. The geometric checks intend to test the treatment isocenter size and its coincidence with imaging devices, the positioning accuracy of the imaging systems, the collimator, the gantry, the jaws, the MLC leaves and the couch position. The dosimetric checks: refer to a reference MV image and give the beam output, uniformity and center change relative to the reference. MPC data were acquired during 10 repetitions on different consecutive days. Alternative independent checks were performed. Geometric: routine mechanical tests, Winston-Lutz test for treatment isocenter radius. Dosimetric: the 2D array StarCheck (PTW) was used just after the MPC data acquisition. RESULTS: Results were analyzed for 6, 10, 15 MV flattened, and 6, 10 MV FFF beams. Geometric checks: treatment isocenter was between 0.31 ± 0.01 mm and 0.42 ± 0.02 mm with MPC, compared to 0.27 ± 0.01 mm averaged on all energies with the Winston-Lutz test. Coincidence of kV and MV imaging isocenters was within 0.36 ± 0.0 and 0.43 ± 0.06 mm, respectively (0.4 ± 0.1 mm with external tests). Positioning accuracy of MLC was within 0.5 mm; accuracy of jaws was 0.04 ± 0.02, 0.10 ± 0.05, -1.01 ± 0.03, 0.92 ± 0.04 mm for X1, X2, Y1, Y2 jaws, respectively, with MPC. Dosimetric tests: the output stability relative to the baseline was in average 0.15 ± 0.07% for MPC to compare with 0.3 ± 0.2% with the independent measurement. CONCLUSIONS: MPC proved to be a reliable, fast and easy to use method for checking the machine performances on both geometric and dosimetric aspects.