Magnetic Resonance Imaging Relaxation Time Research Articles

Magnetic resonance imaging relaxation time measurements of the placenta at 1.5 T

Placental insufficiency is a major cause of fetal growth restriction (FGR) and accumulating evidence indicates several aspects of placental morphology are altered in this condition. MRI provides quantitative indices that may be used in non-invasive assessment of the human placenta, such as relaxation time measurements, T1 and T2. We hypothesised that placental relaxation times relate to alterations in placental tissue morphology and hence may be useful in identifying the changes associated with FGR. We report on the first phase of testing this hypothesis, in a study of women in normal pregnancy. AimsTo assess relaxation time measurements in the placenta in normal pregnancy and correlate these with gestational age and stereological analyses of placental morphology following delivery. Methods30 women underwent MRI examination (1.5 T) between 20 and 41 weeks gestation. Placental T1 and T2 measurements were acquired from a mid-depth placental region, co-localised to a structural scan. Fixed, wax-embedded sections of these placentas collected at delivery were stained with hematoxylin/eosin and subjected to stereological analysis. ResultsPlacental T1 and T2 show a significant negative correlation with gestation, (Pearson correlation p=0.01, 0.03 respectively). 17 placentas were analysed stereologically. In the group as a whole there was no significant correlation between T1 and T2 and morphological features. However, in a subset of 7 pregnancies scanned within a week of delivery, a significant positive correlation was observed between the fibrin volume density and the ratio of fibrin: villous volume densities and T2 (Spearman correlation p=0.02, 0.03 respectively). DiscussionThe correlations between placental T1 and T2 and gestation show that these variables are clearly influenced by changes in placental structure. Fibrin might be a key component but further work is needed to fully elucidate the major structural influences on placental T1 and T2.

Reduction of body iron stores to normal range levels in thalassaemia by using a deferiprone/deferoxamine combination and their maintenance thereafter by deferiprone monotherapy

Iron overload and toxicity is the major cause of morbidity and mortality in thalassaemia patients. New chelating drug protocols are necessary to treat completely transfusional iron overload and eliminate associated toxicity. Appropriate deferiprone/deferoxamine combinations could achieve this goal. A single-centre, single-armed, proof-of-concept study of the combination of deferiprone (75-100 mg/kg/d) and deferoxamine (40-60 mg/kg, at least 3 d per week) was carried out in eight patients with thalassaemia major (four men and four women) for 21-68 months. The patients were previously treated with deferoxamine and had variable serum ferritin [geometric (G) mean ± SD = 1446 ± 1035 μg/L] and magnetic resonance imaging relaxation times T2* cardiac (Gmean ± SD = 10.32 ± 6.72 ms) and liver (G mean ± SD = 3.77 ± 4.69 ms). The use of deferiprone (80-100 mg/kg/d) continued for 7-26 months in seven of the eight patients following the combination therapy. Organ function, blood and other biochemical parameters were monitored for toxicity. The deferiprone/deferoxamine combination caused an absolute value increase in cardiac (G mean ± SD = 29.6 ± 6.6 ms, P < 0.00076) and liver (G mean ± SD = 25.9 ± 8.07 ms, P < 0.00075) T2* and reduction in serum ferritin (G mean ± SD = 114.7 ± 139.8 μg/L, P < 0.0052) to within the normal body iron store range levels. In two cases, normalisation was achieved within a year. Deferiprone monotherapy was sufficient thereafter in maintaining normal range cardiac (G mean ± SD = 31.4 ± 5.25 ms, P < 0.79) and liver (G mean ± SD = 26.2 ± 12.4 ms, P < 0.58) T2* and normal serum ferritin (G mean ± SD = 150.7 ± 159.1, μg/L, P < 0.17) in five of the seven patients. No serious toxicity was observed. Transfusional iron overload in patients with thalassaemia could be reduced to normal body iron range levels using effective deferiprone/deferoxamine combinations. These levels could be maintained using deferiprone monotherapy.

Uses and Limitations of Serum Ferritin, Magnetic Resonance Imaging T2 and T2* in the Diagnosis of Iron Overload and in the Ferrikinetics of Normalization of the Iron Stores in Thalassemia Using the International Committee on Chelation Deferiprone/Deferoxamine Combination Protocol

Excess cardiac iron deposition leads to congestive cardiac failure and accounts for more than 70% of deaths in thalassemia major patients. In three separate studies involving 145 thalassemia patients, serum ferritin and magnetic resonance imaging (MRI) relaxation times T2 and T2* have been compared for assessing iron load levels during chelation treatment. In two studies, variable levels of cardiac iron load have been detected by T2 and T2* in patients treated with deferoxamine (DFO), which, however, were unrelated to serum ferritin. In most cases, similar range levels from normal to severe cardiac iron load could be identified by both the T2 and T2* methods. However, in a few cases there were substantial differences in the levels detected between the two methods. In the third study, the ferrikinetics of the normalization of the iron stores during the International Committee on Chelation (ICOC) deferiprone (L1)/DFO combination protocol was followed up using T2 and T2* and serum ferritin. Iron deposits were found not to be proportionally distributed between the liver and the heart or uniformly distributed within each organ. Iron mobilization in each patient varied and iron deposits in each organ were cleared at different rates. Despite some limitations, the application of the MRI relaxation times T2 and T2* offers the best diagnostic methods for iron overload estimations in most organs and especially the heart. These MRI methods and serum ferritin could also be used for the ferrikinetics of iron mobilization and removal during chelation therapy and the normalization of the iron stores during the ICOC L1/DFO combination protocol. There is a need to standardize the two MRI relaxation times T2 and T2* methods and identify the factors causing the differences between them.

ADVANCED MAGNETIC RESONANCE IMAGING OF CEREBRAL CAVERNOUS MALFORMATIONS

We hypothesized that structural details that have not been described previously would be revealed in cerebral cavernous malformations (CCM) through the use of high-field magnetic resonance and confocal microscopy. The structural details of CCMs excised from patients were sought by examination with high-field magnetic resonance imaging (MRI) and correlated with confocal microscopy of the same specimens. Novel features of CCM structure are outlined, including methodological limitations, venues for future research, and possible clinical implications. CCM lesions excised from 4 patients were fixed in 2% paraformaldehyde and subjected to high-resolution MRI at 9.4 or 14.1-T by spin echo and gradient recalled echo methods. Histological validation of angioarchitecture was conducted on thick sections of CCM lesions using fluorescent probes to endothelium under confocal microscopy. Images of excised human CCM lesions were acquired with proton density-weighted, T1-weighted, T2-weighted spin echo, and T2*-weighted gradient recalled echo MRI. These images revealed large "bland" regions with thin-walled caverns and "honeycombed" regions with notable capillary proliferation and smaller caverns surrounding larger caverns. Proliferating capillaries and caverns of various sizes were also associated with the walls of apparent larger blood vessels in the lesions. Similar features were confirmed within thick sections of CCMs by confocal microscopy. MRI relaxation times in different regions of interest suggested the presence of different states of blood breakdown products in areas with apparent angiogenic proliferative activity. High-field MRI techniques demonstrate novel features of CCM angioarchitecture, visible at near histological resolution, including regions with apparently different biological activity. These preliminary observations will motivate future research, correlating lesion biological and clinical activity with features of MRI at higher field strength.

Changes in Soil Water Content Resulting fromRicinusRoot Uptake Monitored by Magnetic Resonance Imaging

Magnetic resonance imaging (MRI) was used to study the soil water content changes caused by root water uptake. A 4‐wk‐oldRicinus communis carmencitawith a highly developed root system was planted in a cylindrical container filled with a model soil (99.5% fine sand, 0.5% clay), fully water saturated. The bottom and surface of the container were sealed so that water loss by factors other than transpiration via the leaves could be neglected. The water content of the soil was monitored for 3 wk using the MRI sequence SPRITE at an isotropic spatial resolution of 6.3 mm. In contrast to conventionally used MRI sequences, the T2* relaxation was monitored, temporally resolved, and extrapolated to zero. This procedure is a better measure of water content than a single signal at a given time point since it eliminates varying MRI relaxation times during soil desiccation. A linear correlation between the MRI‐determined and gravimetrically measured total water content proves the correctness of the monitoring and data evaluation procedure. Simultaneously, the root architecture was also imaged at 0.6 mm isotropic resolution by the MRI sequence constructive interference in steady state (CISS), which yielded a good contrast between soil and roots. The coregistration of both types of imaging (water content and root architecture) indicates that greater changes in water content took place in the bottom region and near the surface, where the highest root densities were found.

New techniques for cartilage magnetic resonance imaging relaxation time analysis: Texture analysis of flattened cartilage and localized intra‐ and inter‐subject comparisons

MR relaxation time measurements of knee cartilage have shown potential to characterize knee osteoarthritis (OA). In this work, techniques that allow localized intra- and inter-subject comparisons of cartilage relaxation times, as well as cartilage flattening for texture analysis parallel and perpendicular to the natural cartilage layers, are presented. The localized comparisons are based on the registration of bone structures and the assignment of relaxation time feature vectors to each point in the bone-cartilage interface. Cartilage flattening was accomplished with Bezier splines and warping, and texture analysis was performed with second-order texture measures using gray-level co-occurrence matrices (GLCM). In a cohort of five normal subjects the performance and reproducibility of the techniques were evaluated using T1rho maps of femoral knee cartilage. The feasibility of creating a mean cartilage relaxation time map is also presented. Successful localized intra- and inter-subject T1rho comparisons were obtained with reproducibility similar to that reported in the literature for regional T2. Improvement of the reproducibility of GLCM features was obtained by flattening the T1rho maps. The results indicate that the presented techniques have potential in longitudinal and population studies of knee OA at different stages of the disease.

Fluorescent Bacterial Magnetic Nanoparticles as Bimodal Contrast Agents

The purpose of this study was to assess whether fluorochrome-coupled bacterial magnetic nanoparticles can be used as bimodal contrast agent for both magnetic resonance imaging (MRI) and near-infrared fluorescence optical (NIRF) imaging of cultured macrophages. Bacterial magnetic nanoparticles (magnetosomes, particle diameter: 42 nm) were harvested from Magnetospirillum gryphiswaldense and characterized by using MRI. After covalent coupling to the fluorescent dye DY-676 (lambdaabs./lambdaem.= 676 nm/701 nm, Dyomics, Jena, Germany), the fluorescent magnetosomes were analyzed by fluorescence-activated cell sorting. Subsequently, murine macrophages J774 were incubated with the bimodal contrast agent (3 hours) and examined by a whole-body near infrared small animal imaging system as well as by using a 1.5 T clinical MR system. Moreover, labeled cells were characterized using confocal laser scanning microscopy (CLSM) and ultrathin section transmission electron microscopy. Characterization of the nanoparticles by MRI revealed R1 and R2 relaxivities of 3.2 mMs and 526 mMs, respectively. Fluorochrome-coupled magnetosomes exhibited increased fluorescence intensities at wavelengths >670 nm. Macrophages that were incubated with the contrast agent showed a significant fluorescence emission in the near infrared range as imaged with a whole body NIR imaging system, FACS analysis and CLSM. Moreover, CLSM data showed the greatest fluorescence intensities within intracellular compartments and colocalized with the magnetosomes. With MRI, both T1 and T2 relaxation times were substantially shortened at concentrations greater than 600 cells/microL. Macrophages could be labeled with fluorescent magnetosomes, and they were successfully imaged using both a 1.5 T MR scanner as well as with NIRF optical methods. The use of this bimodal contrast agent for diagnostic purposes may benefit from the excellent spatial resolution of the MRI and the high sensitivity of the fluorescence imaging.

Early gene therapy-induced apoptotic response in BT4C gliomas by magnetic resonance relaxation contrast T1 in the rotating frame.

The design and evaluation of therapeutic gene transfection protocols and vectors are under extensive development. Magnetic resonance imaging (MRI) techniques can aid considerably in the development of experimental treatment approaches, as well as in determining treatment response by observing gross tissue morphology. However, through a unique set of contrast parameters, namely T1, T2, and diffusion, more information about tissue status can be obtained while delineating and classifying tumor characteristics in more detail. We show here that T1 relaxation in the rotating frame, T1rho, provides unique in vivo MRI contrast. Ganciclovir treatment of HSV-tk+BT4C gliomas, which effectively eradicates these tumors, resulted in significantly prolonged T1rho relaxation times in MRI already after 3 days of treatment, whereas conventional contrast parameters were elevated after 6-8 days of therapy. Interestingly, the prolonged T1rho values were observed while an increase in tumor volume was still taking place. The regions of elevated T1rho relaxation coincided with high apoptotic activity as determined by histology, suggesting that T1rho MRI contrast could be used as a novel early indicator of cytotoxic cell damage in gliomas.

Early detection of irreversible cerebral ischemia in the rat using dispersion of the magnetic resonance imaging relaxation time, T1rho.

The impact of brain imaging on the assessment of tissue status is likely to increase with the advent of treatment methods for acute cerebral ischemia. Multimodal magnetic resonance imaging (MRI) demonstrates potential for selecting stroke therapy patients by identifying the presence of acute ischemia, delineating the perfusion defect, and excluding hemorrhage. Yet, the identification of tissue subject to reversible or irreversible ischemia has proven to be difficult. Here, the authors show that T1 relaxation time in the rotating frame, so-called T1rho, serves as a sensitive MRI indicator of cerebral ischemia in the rat. The T1rho prolongs within minutes after a drop in the CBF of less than 22 mL 100 g(-1) min(-1). Dependence of T1rho on spin-lock amplitude, termed as T1rho dispersion, increases by approximately 20% on middle cerebral artery (MCA) occlusion, comparable with the magnitude of diffusion reduction. The T1rho dispersion change dynamically increases to be 38% +/- 10% by the first 60 minutes of ischemia in the brain region destined to develop infarction. Following reperfusion after 45 minutes of MCA occlusion, the tissue with elevated T1rho dispersion (yet normal diffusion) develops severe histologically verified neuronal damage; thus, the former parameter unveils an irreversible condition earlier than currently available MRI methods. The T1rho dispersion as a novel MRI index of cerebral ischemia may be useful in determination of the therapeutic window for acute ischemic stroke.

Enhancing Web applications in radiology with Java: estimating MR imaging relaxation times.

Java is a relatively new programming language that has been used to develop a World Wide Web-based tool for estimating magnetic resonance (MR) imaging relaxation times, thereby demonstrating how Java may be used for Web-based radiology applications beyond improving the user interface of teaching files. A standard processing algorithm coded with Java is downloaded along with the hypertext markup language (HTML) document. The user (client) selects the desired pulse sequence and inputs data obtained from a region of interest on the MR images. The algorithm is used to modify selected MR imaging parameters in an equation that models the phenomenon being evaluated. MR imaging relaxation times are estimated, and confidence intervals and a P value expressing the accuracy of the final results are calculated. Design features such as simplicity, object-oriented programming, and security restrictions allow Java to expand the capabilities of HTML by offering a more versatile user interface that includes dynamic annotations and graphics. Java also allows the client to perform more sophisticated information processing and computation than is usually associated with Web applications. Java is likely to become a standard programming option, and the development of stand-alone Java applications may become more common as Java is integrated into future versions of computer operating systems.

Noninvasive detection of cerebral hypoperfusion and reversible ischemia from reductions in the magnetic resonance imaging relaxation time, T2.

The hypothesis was tested that hypoperfused brain regions, such as the ischemic penumbra, are detectable by reductions in absolute transverse relaxation time constant (T2) using magnetic resonance imaging (MRI). To accomplish this, temporal evolution of T2 was measured in several models of hypoperfusion and focal cerebral ischemia in the rat at 9.4 T. Occurrence of acute ischemia was determined through the absolute diffusion constant D(av) = 1/3 TraceD, while perfusion was assessed by dynamic contrast imaging. Three types of regions at risk of infarction could be distinguished: (1) areas with reduced T2 (4% to 15%, all figures relative to contralateral hemisphere) and normal D(av), corresponding to hypoperfusion without ischemia; (2) areas with both reduced T2 (4% to 12%) and D(av) (22% to 49%), corresponding to early hypoperfusion with ischemia; (3) areas with increased T2 (2% to 9%) and reduced D(av) (28% to 45%), corresponding to irreversible ischemia. In the first two groups, perfusion-deficient regions detected by bolus tracking were similar to those with initially reduced T2. In the third group, bolus tracking showed barely detectable arrival of the tracer in the region where D(av) was reduced. We conclude that T2 reduction in acute ischemia can unambiguously identify regions at risk and potentially discriminate between reversible and irreversible hypoperfusion and ischemia.

Magnetic resonance imaging techniques for monitoring changes in tumor oxygenation and blood flow

The application of functional magnetic resonance (MR) imaging techniques to the measurement of oxygenation and blood flow in tumors is described. Gradient recalled echo MR imaging (GRE-MRI) offers a real-time noninvasive method for monitoring tumor response to vasomodulators such as carbogen (95% O2/5% CO2) breathing in attempts to overcome tumor hypoxia and improve treatment efficacy. Although the response is tumor-type dependent, increases in signal intensity of up to 100% have been observed in several animal tumor types. Responses are also seen in human tumors. The observed increases in GRE-MRI signal intensity are due to a combination of a reduction of deoxyhemoglobin in the blood causing changes in the MR imaging relaxation time T2* and changes in blood flow and may also reflect the capillary density. Thus, the magnitude of the GRE image intensity change gives an indication of the potential response of an individual tumor to treatments that aim to improve tissue oxygenation and therefore how the tumor may respond to therapy. In addition, carbogen breathing by the host has been shown to increase the uptake and efficacy of chemotherapeutic agents in animal tumors.

Skeletal muscle of patients with gyrate atrophy of the choroid and retina and hyperornithinaemia in ultralow-field magnetic resonance imaging and computed tomography.

Gyrate atrophy of the choroid and retina with hyperornithinaemia (GA), an autosomal recessive disease, affects skeletal muscle in addition to the eye. Muscle biopsy samples show prominent type 2 muscle fibre atrophy. Atrophic fibres also contain accumulations of tubular aggregates in electron microscopy. To evaluate skeletal muscle involvement in detail, the thigh muscles of 7 patients with GA were examined using semi-open conchotome muscle biopsies, computed tomography (CT) and ultralow-field magnetic resonance imaging (MRI) at 0.02 T. In MRI, the T1 and T2 proton relaxation times were measured. Type 2 muscle fibre atrophy was found in all biopsy samples (100%) and tubular aggregates in 6 of the 7 samples studied (87%). The CT density of the muscle tissue was increased in the only child of the study, decreased in 3 elderly subjects, and normal in the remaining 3 patients. Mean T1 relaxation times of the patients were decreased (135 +/- 5 ms) as compared to those of 6 healthy controls (157 +/- 12 ms) (p = 0.002). The T2 relaxation time was slightly increased (40 +/- 3 ms) as compared to the controls (35 +/- 7 ms; not significant, p = 0.3). Our findings suggest that the thigh muscles of the patients with GA universally show changes in CT and MRI studies, but relaxation time measurements gave little additional information on the muscle metabolism.

Relationship between MRI relaxation time and muscle fiber composition.

The relationship between nuclear magnetic resonance relaxation time obtained with magnetic resonance imaging (MRI) and muscle fiber composition of the lateral gastrocnemius was examined in 13 men. There was a positive correlation (r = 0.80, P < or = 0.001) between longitudinal relaxation time and the relative percentage of slow-twitch muscle fibers (type I). There was no relationship between transverse relaxation time and type I percentage (r = 0.17, P = 0.57). These results suggest that MRI longitudinal relaxation time can be used for the noninvasive estimation of muscle fiber composition in humans.

Bone marrow diseases of the spine: differentiation with T1 and T2 relaxation times in MR imaging.

Forty-two patients underwent magnetic resonance (MR) imaging for a variety of lesions in the vertebral body. A 0.15-T MR system was employed. Twenty-six patients were found to have malignant metastatic lesions (group 1); 16 had nonneoplastic lesions (group 2). The ability to differentiate between the two groups with MR imaging was evaluated. With the longer spin-echo repetition time, the image was variable in both groups. All malignant metastatic lesions appeared as low-intensity areas on T1-weighted images, but 50% of the nonneoplastic lesions also appeared this way. The mean T1 for group 1 was longer than that for group 2, but not significantly so. However, there were significant differences in the ratios of T1 to T2 and of the T1 ratio to the T2 ratio (T1 ratio = T1 for affected vertebrae/T1 for normal vertebrae, T2 ratio = T2 for affected vertebrae/T2 for normal vertebrae). These ratios were therefore useful in distinguishing malignant metastatic from nonneoplastic lesions.