Magnetic Resonance Imaging Readouts Research Articles

Molecular MRI Identifies Sexually Dimorphic AD Pathology in 3x Tg‐AD Mice

AbstractBackgroundWomen exhibit higher prevalence of Alzheimer’s disease (AD) with faster cognitive decline compared to men, but the mechanisms of this dimorphism remain understudied. Astrocyte function and morphology is distinct in some regions of male and female adult brains which may reflect different courses taken by the neurodegenerative process. Additionally, the p‐tau levels are higher in females than in males. The 3xTg AD mouse model, which manifests amyloid and tau pathology, has been reported to exhibit similar sexual dimorphism. In this work, we investigated whether molecular MRI using a targeted agent that detects hyperphosphorylative cells expressing cell‐surface vimentin predominantly on neurons and the disease associated astrocytes in early states of tau pathology can be used for in vivo imaging of sexual dimorphism in AD pathology.MethodLiposomal Withaferin nanoparticles (WNP) that contain Gd/DOTA for an MRI readout were injected in 3xTg AD mice, at 2‐,5‐,7‐ 9‐ and 12‐ months of age. Animals (n = 14/timepoint, 7 males and 7 females) underwent contrast enhanced magnetic resonance imaging (MRI) using T1 weighted sequences to visualize hyperphosphorylative cells expressing cell surface vimentin. Animals were euthanized after the final time point and brains were harvested for histology and immunofluorescence analysis. CE‐MR images were analyzed for signal enhancement.ResultIn this study, we report the sexually dimorphic nature of the cell surface vimentin expressed by the hyperphosphorylative cells in the brain using the 3xTg AD mice. Both sexes were imaged at 2‐,5‐,7‐ and 9‐ months of age to reveal significant differences in the expression of VIM in males and . Signal enhancement in post‐contrast MRI scans over the baseline scans showed significantly higher enhancement in the females compared with the males (p<0.05) Simultaneously, we also investigate the plasma concentrations of total tau, ptau181, amyloid beta 40 and 42.ConclusionFemale mice expressed higher vimentin in comparison with males, thus reflecting changes in the neurodegenerative processes in the brains of females and males of this strain. Sexually dimorphic molecular changes were successfully visualized by molecular MRI.

Plasma pTau markers correlate with an imaging surrogate marker of hyperphosphorylation in mouse models of Alzheimers disease

AbstractBackgroundWe previously reported Cell surface vimentin (CSV) as a surrogate marker for cells in a hyperphosphorylative state, leading to pathological tau deposits in mouse models. Here were investigate the correlation between a Magnetic Resonance Imaging (MRI) marker of CSV and changes in the plasma pTau biomarkers at early stages of tau pathology. We studied total tau, ptau181 and ptau 231 in the plasma of mice at 2 and 5months of age prior to the formation of frank pathology, and with emerging pathology respectively, and compared them to the signal from the MRI marker of CSV.MethodTransgenic P301S and APP/PSEN1 mice and their wild‐type littermates were injected intravenously with liposomal nanoparticles bearing small molecule Withaferin (WNP) as a targeting ligand, and Gd/DOTA as an MRI readout, at 2‐ and 5‐ months of age. Animals (n=10 each) underwent magnetic resonance imaging (MRI) using T1 weighted sequences to visualize brain localization of CSV‐targeted liposomes. Blood was collected in EDTA tubes by puncture of facial vein post‐MRI scan. Plasma samples were centrifuged at 1000xg for 10mins at 4⁰C within 30mins of collection and stored at ‐80⁰C. Plasma concentrations of tau species were measured using the multiplex xMAP Luminex platform with kit‐based reagents, Milliplex for ptau181, total tau and Procartaplex for ptau231.ResultMRI signal enhancement was observed in 2‐month old transgenic mice but not in WT mice in both P301S and APP/PSEN1 AD models. Concurrently, we observed higher expression of ptau 181 in the TG mice over WT littermates. Similar results were also observed in the 5‐month old mice.ConclusionMRI with CSV targeted nanoparticles demonstrates brain signal that correlates with pTau181, consistent with the cell surface marker of hyperphosphorylation marking the same process that results in hyperphosphorylated tau species being formed in the transgenic mice. The results strengthen the mechanistic basis of a cell‐surface vimentin targeted agent being a suitable marker of very early‐stage development of tau pathology and furthermore demonstrates localization of the pathology. The use of readily available and relatively inexpensive MRI for this purpose has huge advantages over existing methods for the identification of early stage tau pathology.

Designing Protein-Based Probes for Sensing Biological Analytes with Magnetic Resonance Imaging.

Genetically encoded sensors provide unique advantages for monitoring biological analytes with molecular and cellular-level specificity. While sensors derived from fluorescent proteins represent staple tools in biological imaging, these probes are limited to optically accessible preparations owing to physical curbs on light penetration. In contrast to optical methods, magnetic resonance imaging (MRI) may be used to noninvasively look inside intact organisms at any arbitrary depth and over large fields of view. These capabilities have spurred the development of innovative methods to connect MRI readouts with biological targets using protein-based probes that are in principle genetically encodable. Here, we highlight the state-of-the-art in MRI-based biomolecular sensors, focusing on their physical mechanisms, quantitative characteristics, and biological applications. We also describe how innovations in reporter gene technology are creating new opportunities to engineer MRI sensors that are sensitive to dilute biological targets.

Extent of Cord Pathology in the Lumbosacral Enlargement in Non-Traumatic versus Traumatic Spinal Cord Injury.

This study compares remote neurodegenerative changes caudal to a cervical injury in degenerative cervical myelopathy (DCM; i.e., non-traumatic) and incomplete traumatic spinal cord injury (tSCI) patients, using magnetic resonance imaging (MRI)-based tissue area measurements and diffusion tensor imaging (DTI). Eighteen mild-to-moderate DCM patients with sensory impairments (modified Japanese Orthopedic score: 16.2 ± 1.9), 14 incomplete tetraplegic tSCI patients (American Spinal Injury Association Impairment Scale C and D), and 20 healthy controls were recruited. All participants received DTI and T2*-weighted scans in the lumbosacral enlargement (caudal to injury) and at C2/C3 (rostral to injury). MRI readouts included DTI metrics in the white matter (WM) columns and cross-sectional WM and gray matter area. One-way analysis of variance with Tukey's post hoc comparison (p < 0.05) was used to assess group differences. In the lumbosacral enlargement, compared with DCM, tSCI patients exhibited decreased fractional anisotropy in the lateral (tSCI vs. DCM, -11.9%, p = 0.007) and ventral WM column (-8.0%, p = 0.021), and showed a trend toward lower values in the dorsal column (-8.9%, p = 0.068). At C2/C3, compared with controls, fractional anisotropy was lower in both groups in the dorsal (DCM vs. controls, -7.9%, p = 0.024; tSCI vs. controls, -10.0%, p = 0.007) and in the lateral column (DCM: -6.2%, p = 0.039; tSCI: -13.3%, p < 0.001), while tSCI patients had lower fractional anisotropy than DCM patients in the lateral column (-7.6%, p = 0.029). WM areas were not different between patient groups but were lower compared with controls in the lumbosacral enlargement (DCM: -16.9%, p < 0.001; tSCI: -10.5%, p = 0.043) and at C2/C3 (DCM: -16.0%, p < 0.001; tSCI: -18.1%, p < 0.001). In conclusion, mild-to-moderate DCM and incomplete tSCI lead to similar degree of degeneration of the dorsal and lateral columns at C2/C3, but tSCI results in more widespread white matter damage in the lumbosacral enlargement. These remote changes are likely to contribute to the patients' impairment and recovery. DTI is a sensitive tool to assess remote pathological changes in DCM and tSCI patients.

MRI as First Line Imaging for Suspected Acute Appendicitis during Pregnancy: Diagnostic Accuracy and level of Inter-Radiologist Agreement

ObjectiveEvaluation of acute appendicitis (AA) in pregnancy is supported with diagnostic imaging. Typically, ultrasound (US) is performed first, and then often followed by magnetic resonance imaging (MRI) due to continued diagnostic uncertainty. The purpose of our study was to evaluate the sensitivity, specificity, and accuracy of US as compared to MRI and to evaluate the inter-radiologist agreement amongst body Radiologists with varying levels of expertise. Materials and MethodsWe performed a retrospective study of 364 consecutive pregnant patients with clinical suspicion of AA at a single center over a 6-year period. Sensitivity, Specificity, accuracy, positive and negative predictive values were calculated for US and MRI. Inter Radiologist agreement was determined using Cohen's Kappa analysis between original interpreting Radiologist and retrospective review by expert Radiologist. ResultsThirty-one of 364 patients (8.5%) underwent appendectomy based on preoperative diagnosis, with confirmation of acute appendicitis (AA) by pathology in 19. US was able to visualize the appendix in only 6 (1.65%), 5 of whom had appendicitis. 141 patients underwent MRI, and correctly diagnosed appendicitis in 9. No patient with a negative MRI diagnosis had AA. The sensitivity, and negative predictive value for diagnosing AA with MRI was 100%. The MRI inter-reader agreement for appendix visualization and overall accuracy were 87.9 and 98% with Cohen Kappa of 0.7 and 0.56 respectively. ConclusionsOur data suggests that MRI should be considered the first line imaging modality in pregnant patients suspected of having AA. Body Radiologists with varied levels of experience in MRI readouts had substantial agreement.

Diffusion-weighted magnetic resonance imaging (MRI) without susceptibility artifacts: single-shot stimulated echo acquisition mode (STEAM) MRI with iterative reconstruction and spatial regularization.

This work describes a new method for diffusion-weighted (DW) magnetic resonance imaging (MRI) without susceptibility artifacts. The technique combines a DW spin-echo module and a single-shot stimulated echo acquisition mode (STEAM) MRI readout with undersampled radial trajectories and covers a volume by a gapless series of cross-sectional slices. In a first step, optimal coil sensitivities for all slices are obtained from a series of non-DW acquisitions by nonlinear inverse reconstruction with regularization to the image and coil sensitivities of a directly neighboring slice. In a second step, these coil sensitivities are used to compute all series of non-DW and DW images by linear inverse reconstruction with spatial regularization to a neighboring image. Proof-of-principle applications to the brain (51 sections) and prostate (31 sections) of healthy subjects were realized for a protocol with two b-values and 6 gradient directions at 3 T. Including averaging the measuring times for studies of the brain at 1.0×1.0×3.0 mm3 resolution (b =1,000 s mm-2) and prostate at 1.4×1.4×3.0 mm3 resolution (b =600 s mm-2) were 2.5 min and 4.5 min, respectively. All reconstructions were accomplished online with use of a multi-GPU computer integrated into the MRI system. The resulting non-DW images, mean DW images averaged across directions and maps of the apparent diffusion coefficient confirm the absence of geometric distortions or false signal alterations and demonstrate diagnostic image quality. The novel method for DW STEAM MRI of a volume without susceptibility artifacts warrants extended clinical trials.

Tumor grafts grown on the chicken chorioallantoic membrane are distinctively characterized by MRI under functional gas challenge

Recently, a tumor model based on the chorioallantoic membrane (CAM) was characterized structurally with Magnetic Resonance Imaging (MRI). Yet, capability of MRI to assess vascular functional reserve and potential of oxygenation-sensitive MRI remain largely unexplored in this model. For this purpose, we compared MC-38 colon and A549 lung adenocarcinoma cell grafts grown on the CAM, using quantitative T1 and T2* MRI readouts as imaging markers. These are associated with vascular functionality and oxygenation status when compared between periods of air and carbogen exposure. Our data show that in A549 lung adenocarcinoma cell grafts T2* values increased significantly upon carbogen exposure (p < 0.004, Wilcoxon test; no change in T1), while MC-38 grafts displayed no changes in T1 and T2*), indicating that the grafts differ in their vascular response. Heterogeneity with regard to T1 and T2* distribution within the grafts was noted. MC-38 grafts displayed larger T1 and T2* in the graft centre, while in A549 they were distributed more towards the graft surface. Finally, qualitative assessment of gadolinium-enhancement suggests that A549 grafts display more prominent enhancement compared to MC-38 grafts. Furthermore, MC-38 grafts had 65% larger volumes than A549 grafts. Histology revealed distinct underlying phenotypes of the two tumor grafts, pertaining to the proliferative status (Ki-67) and cellularity (H&E). In sum, a functional gas challenge with carbogen is feasible through gas exchange on the CAM, and it affects MRI signals associated with vascular reactivity and oxygenation status of the tumor graft planted on the CAM. Different grafts based on A549 lung adenocarcinoma and MC-38 colon carcinoma cell lines, respectively, display distinct phenotypes that can be distinguished and characterized non-invasively in ovo using MRI in the living chicken embryo.

In Brief

Evaluation of acute appendicitis (AA) in pregnancy is supported with diagnostic imaging. Typically, ultrasound (US) is performed first, and then often followed by magnetic resonance imaging (MRI) due to continued diagnostic uncertainty. The purpose of our study was to evaluate the sensitivity, specificity, and accuracy of US as compared to MRI and to evaluate the inter-radiologist agreement amongst body Radiologists with varying levels of expertise.We performed a retrospective study of 364 consecutive pregnant patients with clinical suspicion of AA at a single center over a 6-year period. Sensitivity, Specificity, accuracy, positive and negative predictive values were calculated for US and MRI. Inter Radiologist agreement was determined using Cohen's Kappa analysis between original interpreting Radiologist and retrospective review by expert Radiologist.Thirty-one of 364 patients (8.5%) underwent appendectomy based on preoperative diagnosis, with confirmation of acute appendicitis (AA) by pathology in 19. US was able to visualize the appendix in only 6 (1.65%), 5 of whom had appendicitis. 141 patients underwent MRI, and correctly diagnosed appendicitis in 9. No patient with a negative MRI diagnosis had AA. The sensitivity, and negative predictive value for diagnosing AA with MRI was 100%. The MRI inter-reader agreement for appendix visualization and overall accuracy were 87.9 and 98% with Cohen Kappa of 0.7 and 0.56 respectively.Our data suggests that MRI should be considered the first line imaging modality in pregnant patients suspected of having AA. Body Radiologists with varied levels of experience in MRI readouts had substantial agreement.

Tracking sensory system atrophy and outcome prediction in spinal cord injury.

ObjectiveIn patients with subacute spinal cord injury (SCI), the motor system undergoes progressive structural changes rostral to the lesion, which are associated with motor outcome. The extent to which the sensory system is affected and how this relates to sensory outcome are uncertain.MethodsChanges in the sensory system were prospectively followed by applying a comprehensive magnetic resonance imaging (MRI) protocol to 14 patients with subacute traumatic SCI at baseline, 2 months, 6 months, and 12 months after injury, combined with a full neurological examination and comprehensive pain assessment. Eighteen controls underwent the same MRI protocol. T1‐weighted volumes, myelin‐sensitive magnetization transfer saturation (MT), and longitudinal relaxation rate (R1) mapping provided data on spinal cord and brain morphometry and microstructure. Regression analysis assessed the relationship between MRI readouts and sensory outcomes.ResultsAt 12 months from baseline, sensory scores were unchanged and below‐level neuropathic pain became prominent. Compared with controls, patients showed progressive degenerative changes in cervical cord and brain morphometry across the sensory system. At 12 months, MT and R1 were reduced in areas of structural decline. Sensory scores at 12 months correlated with rate of change in cord area and brain volume and decreased MT in the spinal cord at 12 months.InterpretationThis study has demonstrated progressive atrophic and microstructural changes across the sensory system with a close relation to sensory outcome. Structural MRI protocols remote from the site of lesion provide new insights into neuronal degeneration underpinning sensory disturbance and have potential as responsive biomarkers of rehabilitation and treatment interventions. Ann Neurol 2015;78:Ann Neurol 2015;78:679–696

Effect of surface coating on the biocompatibility and in vivo MRI detection of iron oxide nanoparticles after intrapulmonary administration

Superparamagnetic iron oxide nanoparticles (SPIONs) have attracted special attention as novel nanoprobes capable of improving both the therapy and diagnosis of lung diseases. For safe prospective clinical applications, their biocompatibility has to be assessed after intrapulmonary administration. This study was therefore conducted to understand the biological impact of SPIONs and their further surface-functionalization with polyethylene glycol (PEG) having either negative (i.e. carboxyl) or positive (i.e. amine) terminal in a 1-month longitudinal study following acute and sub-acute exposures. Noninvasive free-breathing MR imaging protocols were first optimized to validate SPIONs detection in the lung and investigate possible subsequent systemic translocation to abdominal organs. Pulmonary Magnetic Resonance Imaging (MRI) allowed successful in vivo detection of SPIONs in the lung using ultra-short echo time sequence. Following high-dose lung administration, MR imaging performed on abdominal organs detected transient accumulation of SPIONs in the liver. Iron quantification using Inductive coupled plasma – Mass mass spectroscopy (ICP-MS) confirmed MRI readouts. Oxidative stress induction and genotoxicity were then conducted to evaluate the biocompatibility of SPIONs with their different formulations in a mouse model. A significant increase in lipid peroxidation was observed in both acute and sub-acute sets and found to regress in a time-dependent manner. PEG functionalized SPIONs revealed a lower effect with no difference between both terminal modifications. Genotoxicity assessments revealed an increase in DNA damage and gene expression of CCL-17 and IL-10 biomarkers following SPIONs administration, which was significantly higher than surface-modified nanoparticles and decreased in a time-dependent manner. However, SPIONs with carboxyl terminal showed a slightly prominent effect compared to amine modification.

Enhanced magnetic delivery of superparamagnetic iron oxide nanoparticles to the lung monitored using noninvasive MR

This study aimed to improve the targeting of superparamagnetic iron oxide nanoparticles (SPIONs) to the lung after intravenous administration. In order to achieve a higher pulmonary delivery, high-energy flexible magnets were optimized and externally applied to a specific region of mouse lung. SPIONs and magnets were first characterized, and a free-breathing magnetic resonance imaging (MRI) protocol was then optimized to allow noninvasive monitoring and for their sensitive detection to the target site in the lung, using an ultrashort time of echo radial MR pulse sequence. In addition, histological analysis using Perls’ staining and iron quantification using inductive couple plasma-mass spectroscopy (ICP-MS) were performed to confirm MRI readouts. A flexible magnet with inverse multiple polarities was found to enhance the magnetic targeting of SPIONs to the lung. MRI readouts enabled successful detection of enhanced SPION migration to the lower right lobe, where the magnet was positioned. Attracted by the magnet, SPIONs were found to accumulate in the lung tissue within 2 h post-injection as seen in histological images and through ICP-MS, where a notable increase in iron concentrations were observed in the magnet group compared to control mice. In conclusion, the external application of an optimized high-energy magnet with multiple polarities over specific regions of the lung enhanced the magnetic targeting of SPIONs to the site of interest within the lung after intravenous injection.

MR imaging and targeting of a specific alveolar macrophage subpopulation in LPS-induced COPD animal model using antibody-conjugated magnetic nanoparticles

PurposeTargeting and noninvasive imaging of a specific alveolar macrophage subpopulation in the lung has revealed the importance for early and better diagnosis and therapy of chronic obstructive pulmonary disease (COPD). In this study, the in vivo effect of pulmonary administration of iron oxide nanoparticles on the polarization profile of macrophages was assessed, and a noninvasive free-breathing magnetic resonance imaging (MRI) protocol coupled with the use of biocompatible antibody-conjugated superparamagnetic iron oxide (SPIO) nanoparticles was developed to enable specific targeting and imaging of a particular macrophage subpopulation in lipopolysaccharide-induced COPD mice model.Materials and methodsEnzyme-linked immunosorbent assay, Real-time polymerase chain reaction, and flow cytometry analysis were performed to assess the biocompatibility of PEGylated dextran-coated SPIO nanoparticles. Specific biomarkers for M1 and M2 macrophages subsets were selected for conjugation with magnetic nanoparticles. MRI protocol using ultra-short echo time sequence was optimized to enable simultaneous detection of inflammation progress in the lung and detection of macrophages subsets. Flow cytometry and immunohistochemistry analysis were finally performed to confirm MRI readouts and to characterize the polarization profile of targeted macrophages.ResultsThe tested SPIO nanoparticles, under the current experimental conditions, were found to be biocompatible for lung administration in preclinical settings. Cluster of differentiation (CD)86- and CD206-conjugated magnetic nanoparticles enabled successful noninvasive detection of M1 and M2 macrophage subpopulations, respectively, and were found to co-localize with inflammatory regions induced by lipopolysaccharide challenge. No variation in the polarization profile of targeted macrophages was observed, even though a continuum switch in their polarization might occur. However, further confirmatory studies are required to conclusively establish this observation.ConclusionCoupling of magnetic iron oxide nanoparticles with a specific antibody targeted to a particular macrophage subpopulation could offer a promising strategy for an early and better diagnosis of pulmonary inflammatory diseases using noninvasive MRI.

Evaluation of radiochromic gel dosimetry and polymer gel dosimetry in a clinical dose verification

A quantitative comparison of two full three-dimensional (3D) gel dosimetry techniques was assessed in a clinical setting: radiochromic gel dosimetry with an in-house developed optical laser CT scanner and polymer gel dosimetry with magnetic resonance imaging (MRI). To benchmark both gel dosimeters, they were exposed to a 6 MV photon beam and the depth dose was compared against a diamond detector measurement that served as golden standard. Both gel dosimeters were found accurate within 4% accuracy. In the 3D dose matrix of the radiochromic gel, hotspot dose deviations up to 8% were observed which are attributed to the fabrication procedure. The polymer gel readout was shown to be sensitive to B0 field and B1 field non-uniformities as well as temperature variations during scanning. The performance of the two gel dosimeters was also evaluated for a brain tumour IMRT treatment. Both gel measured dose distributions were compared against treatment planning system predicted dose maps which were validated independently with ion chamber measurements and portal dosimetry. In the radiochromic gel measurement, two sources of deviations could be identified. Firstly, the dose in a cluster of voxels near the edge of the phantom deviated from the planned dose. Secondly, the presence of dose hotspots in the order of 10% related to inhomogeneities in the gel limit the clinical acceptance of this dosimetry technique. Based on the results of the micelle gel dosimeter prototype presented here, chemical optimization will be subject of future work. Polymer gel dosimetry is capable of measuring the absolute dose in the whole 3D volume within 5% accuracy. A temperature stabilization technique is incorporated to increase the accuracy during short measurements, however keeping the temperature stable during long measurement times in both calibration phantoms and the volumetric phantom is more challenging. The sensitivity of MRI readout to minimal temperature fluctuations is demonstrated which proves the need for adequate compensation strategies.

In vivo biodistribution and biological impact of injected carbon nanotubes using magnetic resonance techniques

Background:Single-walled carbon nanotubes (SWCNT) hold promise for applications as contrast agents and target delivery carriers in the field of nanomedicine. When administered in vivo, their biodistribution and pharmacological profile needs to be fully characterized. The tissue distribution of carbon nanotubes and their potential impact on metabolism depend on their shape, coating, and metallic impurities. Because standard radiolabeled or fluorescently-labeled pharmaceuticals are not well suited for long-term in vivo follow-up of carbon nanotubes, alternative methods are required.Methods:In this study, noninvasive in vivo magnetic resonance imaging (MRI) investigations combined with high-resolution magic angle spinning (HR-MAS), Raman spectroscopy, iron assays, and histological analysis ex vivo were proposed and applied to assess the biodistribution and biological impact of intravenously injected pristine (raw and purified) and functionalized SWCNT in a 2-week longitudinal study. Iron impurities allowed raw detection of SWCNT in vivo by susceptibility-weighted MRI.Results:A transitional accumulation in the spleen and liver was observed by MRI. Raman spectroscopy, iron assays, and histological findings confirmed the MRI readouts. Moreover, no acute toxicological effect on the liver metabolic profile was observed using the HR-MAS technique, as confirmed by quantitative real-time polymerase chain reaction analysis.Conclusion:This study illustrates the potential of noninvasive MRI protocols for longitudinal assessment of the biodistribution of SWCNT with associated intrinsic metal impurities. The same approach can be used for any other magnetically-labeled nanoparticles.

Design, data management, and population baseline characteristics of the PERFORM magnetic resonance imaging project

Quantitative information from magnetic resonance imaging (MRI) may substantiate clinical findings and provide additional insight into the mechanism of clinical interventions in therapeutic stroke trials. The PERFORM study is exploring the efficacy of terutroban versus aspirin for secondary prevention in patients with a history of ischemic stroke. We report on the design of an exploratory longitudinal MRI follow-up study that was performed in a subgroup of the PERFORM trial. An international multi-centre longitudinal follow-up MRI study was designed for different MR systems employing safety and efficacy readouts: new T2 lesions, new DWI lesions, whole brain volume change, hippocampal volume change, changes in tissue microstructure as depicted by mean diffusivity and fractional anisotropy, vessel patency on MR angiography, and the presence of and development of new microbleeds. A total of 1,056 patients (men and women ≥55 years) were included. The data analysis included 3D reformation, image registration of different contrasts, tissue segmentation, and automated lesion detection. This large international multi-centre study demonstrates how new MRI readouts can be used to provide key information on the evolution of cerebral tissue lesions and within the macrovasculature after atherothrombotic stroke in a large sample of patients.

Fast, three-dimensional, MR Imaging for polymer gel dosimetric applications involving high dose and steep dose gradients

Polymer gels constitute water equivalent integrating detectors, which, combined with magnetic resonance imaging (MRI), can provide accurate three dimensional (3D) dose distributions in contemporary radiotherapy applications where the small field dimensions and steep dose gradients induce limitations to conventional dosimeters. One of the main obstacles for adapting the method for routine use in the clinical setting is the cost effectiveness of the MRI readout method. Currently, optimized Carr-Purcell-Meiboom-Gill (CPMG) multiple spin echo imaging pulse sequences are commonly used which however result in long imaging times. This work evaluates the efficiency of 3D, dual-echo, k-space segmented turbo spin echo (TSE) scanning sequences for accurate dosimetry with sub-millimetre spatial resolution in strenuous radiation therapy applications. PABIG polymer gel dosimeters were irradiated with an 192Ir High Dose Rate brachytherapy source, the 4 mm and 8 mm collimator helmets of a gamma knife unit and a custom made x-knife collimator of 1 cm diameter. Profile and dose distribution measurements using TSE are benchmarked against corresponding findings obtained by the commonly used, but time consuming, CPMG sequence as well as treatment planning calculations, Monte Carlo (MC) simulations and film measurements. The implementation of a high Turbo factor was found to provide comparable accuracy, allowing a 64-fold MRI scan acceleration compared to conventional multi-echo sequences. The availability of TSE sequences in typical MRI installations greatly facilitates the introduction of polymer gel dosimetry in the clinical environment as a practicable tool for the determination of full 3D dose distributions in contemporary radiotherapy applications.

Characterization of CNS disorders and evaluation of therapy using structural and functional MRI.

Modern drug development requires technologies that allow rapid translation from the preclinical to the clinical stage. It is obvious that non-invasive imaging modalities such as magnetic resonance imaging (MRI) will play a central role in this regard. This article reviews the use of structural and functional MRI readouts for characterization of central nervous system (CNS) disorders and evaluation of the efficacy of potential CNS drugs. Examples comprise dementia of Alzheimer's type, cerebral ischemia, and neuroinflammation covering both clinical and preclinical aspects. In these examples MRI has been used to obtain relevant structural information on brain atrophy, on the location and extent of ischemic brain areas, and on the number and distribution of demyelinated plaques. These structural data are complemented by readouts assessing the functional consequences associated with the pathomorphological changes. In the last decade, MRI has evolved into a standard tool for the development of CNS drugs. With regard to target-specific/molecular imaging applications MRI is limited by its inherently low sensitivity; complementary imaging modalities utilizing optical and radionuclear reporter systems will thus be required.