Biomedical subjects

Theodore P Trouard

Publications and source records attributed to Theodore P Trouard.

15 recordsLinked to original sources

PubMed2007

Caffeine attenuates practice effects in word stem completion as measured by fMRI BOLD signal.

Caffeine ingestion results in increased brain cell metabolism (Nehlig et al. [1992] Brain Res Brain Res Rev 17:139-170) and decreased cerebral blood flow (Field et al. [2003] Radiology 227:129-135; Mulderink et al. [2002] Neuroimage 15:37-44). The current study investigated the effect of caffeine in a word stem completion task using only novel word stems (no repeated stimuli). Resting perfusion was measured with arterial spin labeled perfusion MRI, along with blood oxygenation level-dependent (BOLD) signal before and after ingestion of regular coffee, decaffeinated coffee, and water. Based on previous research (Laurienti et al. [2002] Neuroimage 17:751-757; Mulderink et al. [2002] Neuroimage 15:37-44), we hypothesized that caffeine would result in increased BOLD signal intensity and extent of BOLD activation. As expected, caffeine resulted in a significant decrease in cerebral perfusion. However, both the control and caffeine groups showed an increase in BOLD signal amplitude across two sets of novel word stems. Additionally, the control group showed a 50% reduction in the extent of BOLD activation, while the caffeine group showed no change in activation extent. Neither group showed changes in BOLD baseline signal over time, which had been suggested to mediate caffeine-related BOLD signal changes. The results suggest that caffeine may attenuate general task practice effects that have been described in recent functional MRI studies of word stem completion (Buckner et al. [2000] Brain 123:620-640).

Adolescent↗

PubMed2006

Redox-sensitive contrast agents for MRI based on reversible binding of thiols to serum albumin.

DOTA-based complexes of gadolinium (Gd) bearing a thiol moiety on a propyl or hexyl arm were synthesized. It was hypothesized that these complexes would form reversible covalent linkages with human serum albumin (HSA), which contains a reactive thiol at cysteine-34. The binding constant of the hexyl complex to HSA was measured to be 64 mM(-1) and decreased to 17, 6.1, and 3.6 mM(-1) in the presence of 0.5, 1, and 2 mM homocysteine, respectively. The binding constant of the propyl complex to HSA was significantly lower (5.0 mM(-1)) and decreased to 2.0, 1.5, and 0.87 mM(-1) in the presence of 0.5, 1, and 2 mM homocysteine, respectively. The longitudinal water-proton relaxivities of the hexyl and propyl complexes at 37 degrees C and 4.7 T were 2.3 and 2.9 mM(-1) s(-1), respectively, in saline. The relaxivities of the HSA-bound forms of the hexyl and propyl complexes were calculated to be 5.3 and 4.5 mM(-1) s(-1), respectively. The in vivo pharmacokinetics of both thiol complexes were altered by a chase of homocysteine but not saline, while the washout of GdDTPA was unaffected by either chase. Such redox-sensitive reversible binding of Gd complexes to plasma albumin can be exploited for imaging tissue redox and the blood-pool by MRI.

Animals↗

PubMed2005

Allopregnanolone treatment, both as a single injection or repetitively, delays demyelination and enhances survival of Niemann-Pick C mice.

Niemann-Pick C disease (NPC) is an irreversible neurodegenerative disorder without current treatment. It is thought to result from deficient intracellular cholesterol and/or ganglioside trafficking. We have investigated the effects of allopregnanolone treatments on survival, weight loss, motor function, magnetic resonance imaging (MRI), and neuropathology in the mouse model of NPC (Npc1(-/-) mice). We confirmed previous results showing that a single injection of 250 microg of allopregnanolone on postnatal day 7 significantly extended the life span of Npc1(-/-) mice. This caused a marked difference in the weight curves of the treated mice but no statistical difference in the Rota-Rod performance. T2-weighted MRI and diffusion tensor imaging (DTI) of treated mice showed values of signal intensity and fractional anisotropy closer to those of wild-type mice than those of untreated Npc1(-/-) mice. Neuropathology showed that day-7 treatment markedly suppressed astrocyte reaction and significantly reduced microglial activation. Furthermore, the steroid treatment also increased myelination in brains of Npc1(-/-) mice. Similar effects of allopregnanolone treatment were observed in Npc1(-/-), mdr1a(-/-) double-mutant mice, which have a deficient blood-brain barrier, resulting in increased steroid uptake. The effects on survival and weight loss of a single injection on day 7 followed by injections every 2 weeks were also evaluated in Npc1(-/-) mice, and the beneficial effects were found to be greater than with the single injection at day 7. We conclude that allopregnanolone treatment significantly ameliorates several symptoms of NPC in Npc1(-/-) mice, presumably by effects on myelination or neuronal connectivity.

2',3'-Cyclic-Nucleotide Phosphodiesterases↗

PubMed2005

Radial GRASE: implementation and applications.

RAD-GRASE is an MRI sequence that combines radial (RAD) k-space scanning with the gradient and spin-echo (GRASE) technique. RAD-GRASE has the advantages of all radial data acquisition methods in that it can reduce motion sensitivity and correct motion-induced data errors, which can be exploited to achieve high-resolution diffusion-weighted imaging (DWI). One can obtain different types of image contrast, including DWI, T(1), T(2), and T(2)*, in RAD-GRASE by controlling the magnetization preparation and sequence timing. Moreover, because there is oversampling of the low spatial frequencies inherent to radial sequences, partial data reconstruction can be used to achieve multiple forms of image contrast from a single acquired data set, and to generate parametric image maps of equilibrium magnetization, T(2), and T(2) (dagger). The RAD-GRASE technique can also be used to achieve fat-suppressed and/or separated fat and water images by choosing the appropriate timing parameters.

Abdomen↗

PubMed2005

Isotropic diffusion weighting in radial fast spin-echo magnetic resonance imaging.

Radial fast spin-echo (radial-FSE) methods enable multishot diffusion-weighted MRI (DWMRI) to be carried out without significant artifacts due to motion and/or susceptibility and can be used to generate DWMRI images with high spatial resolution. In this work, a novel method that allows isotropic diffusion weighting to be obtained in a single radial k-space data set is presented. This is accomplished by altering the direction of diffusion weighting gradients between groups of TR periods, which yield sets of radial lines that possess diffusion weighting sensitive to motion in different directions. By altering the diffusion weighting directions and controlling the view ordering appropriately within the sequence, an effectively isotropic diffusion-weighted image can be obtained within one radial-FSE scan. The order in which radial lines are acquired can also be controlled to yield data sets without significant artifacts due to motion, T(2) decay, and/or diffusion anisotropy.

Anisotropy↗

PubMed2005

Uncovering of intracellular water in cultured cells.

The complexity of biologic tissues, with multiple compartments each with its own diffusion and relaxation properties, requires complex formalisms to model water signal in most magnetic resonance imaging or magnetic resonance spectroscopy experiments. In this article, we describe a magnetic susceptibility-induced shift in the resonance frequency of extracellular water by the introduction of a gadolinium contrast agent to medium perfusing a hollow fiber bioreactor. The frequency shift of the extracellular water (+185 Hz at 9.4 T) uncovers the intracellular water and allows direct measurement of motional and relaxation properties of the intracellular space. The proposed method provides a unique tool for understanding the mechanisms underlining diffusion and relaxation in the intracellular space.

Animals↗

PubMed2005

Processing of radial fast spin-echo data for obtaining T2 estimates from a single k-space data set.

Radially acquired fast spin-echo data can be processed to obtain T2-weighted images and a T2 map from a single k-space data set. The general approach is to use data at a specific TE (or narrow TE range) in the center of k-space and data at other TE values in the outer part of k-space. With this method high-resolution T2-weighted images and T2 maps are obtained in a time efficient manner. The mixing of TE data, however, introduces errors in the T2-weighted images and T2 maps that affect the accuracy of the T2 estimates. In this work, various k-space data processing methods for reconstructing T2-weighted images and T2 maps from a single radial fast spin-echo k-space data set are analyzed in terms of the accuracy of T2 estimates. The analysis is focused on the effect of image artifacts, object dependency, and noise on the T2 estimates. Results are presented in computer-generated phantoms and in vivo.

Algorithms↗

PubMed2005

Diffusion tensor imaging in Niemann-Pick Type C disease.

Niemann-Pick Type C disease is a homozygous recessive disorder resulting in errant intracellular cholesterol metabolism and the accumulation of intracellular unesterified cholesterol and sphingolipids. Although no current effective treatment exists for Niemann-Pick Type C disease, a number of therapies are under development in animal models. As therapies are brought into clinical trials, it will be extremely helpful to have a reliable means to track the progression of the disease and to monitor its response to therapy. In this effort, diffusion tensor imaging has been applied to investigate the white matter in a Niemann-Pick Type C patient, and the results compared to those from age-matched control subjects. Diffusion tensor imaging enables quantitative measurement of water diffusion in white matter, which is sensitive to the architecture and integrity of the tissue. Compared with control subjects, significant reductions in fractional anisotropy values were observed in regions of white matter, most prominently in the corpus callosum. The results from this case study suggest that diffusion tensor imaging may allow progression of the disease to be quantitatively measured and may be able to play a role as a surrogate marker in clinical trials.

Adolescent↗

PubMed2004

View-ordering in radial fast spin-echo imaging.

Radial MRI sequences are frequently used to obtain images with reduced sensitivity to motion. To decrease imaging time, multiple spin-echo acquisitions can be incorporated into radial sequences. In this case, different radial lines of Fourier data have different TE times and the resulting images can contain streaking artifacts due to T(2) decay. The streaking is not only dependent on the T(2) of the object and the timing of the data acquisition, but also on the order in which radial lines are collected (view order). The view ordering can easily be controlled to minimize artifacts due to T(2) decay as well as motion. Four view-ordering techniques are presented and evaluated for the radial FSE sequence.

Abdomen↗

PubMed2004

Tamoxifen and vitamin E treatments delay symptoms in the mouse model of Niemann-Pick C.

Niemann-Pick C disease (NPC) is an irreversible neurodegenerative disorder without current treatment. It is the result of deficient intracellular cholesterol movement. We investigated the effects of tamoxifen and vitamin E (D-alpha tocopherol) treatment on patterns of weight loss and motor function in the mouse model of Niemann-Pick C disease (Npc1-/- mice). Tamoxifen has multiple metabolic effects, including reducing oxidative damage, while vitamin E primarily has this property. Npc1-/- mice were identified and treatment was initiated at an approximate age of 21 days. Tamoxifen suspended in peanut oil was administered via intraperitoneal injection (weekly, at a dose calculated to deliver 0.023 microg/g/day). Vitamin E (25 IU) was administered orally via gavage once a week. Weight loss and Rota-Rod performance were analyzed by using Kaplan-Meyer survival curves. Tamoxifen treatment by itself significantly delayed weight loss (an endpoint of neurodegeneration) in male and female mice compared to untreated controls. Motor function was evaluated by performance on a Rota-Rod. Tamoxifen maintained Rota-Rod performance for about an extra week. Vitamin E treatment significantly delayed weight loss in females only. Rota-Rod performance was maintained slightly longer in mice treated with vitamin E. Simultaneous use of both treatments did not delay weight loss longer than tamoxifen-only treatment but had a greater effect than either treatment alone on Rota-Rod performance and demonstrated a significant positive effect on the early "learning curve" portion of the Rota-Rod evaluations. We found significant but relatively small improvements in rate of disease progression by treating Npc1-/- mice with tamoxifen and/or vitamin E. Some sex differences in response and an early improvement in Rota-Rod performance suggest areas for further study.

Animals↗

PubMed2003

fMRI variability and the localization of languages in the bilingual brain.

The cerebral localization of multiple languages is a topic of active research. This study presents a method for assessing whether partial overlap of active voxels reflects differential language localization, or simply the variability known to occur with multiple runs of the same task in fMRI studies. Two groups of bilingual subjects (early and later learners of L2) performed word fluency and sentence generation tasks in both languages. The degree of separation for regions of activation did not exceed that associated with run-to-run variability for either task or either group. Early bilinguals, however, showed greater total numbers of active voxels than Late bilinguals for both tasks. This effect occurred despite a lack of a behavioral performance differences by the two groups.

Adolescent↗

PubMed2002

Aphasia severity: Association with cerebral perfusion and diffusion.

BACKGROUND: Previous studies of the relationship between perfusion, diffusion, and stroke suggest that the extent of cerebral hypoperfusion may be a better indicator of neurological status than lesion size in the early phases of recovery. It is not clear how these factors are related to aphasia severity. AIMS: The purpose of this study was to investigate the relationship between cerebral perfusion, diffusion, and aphasia severity in stroke. METHODS #ENTITYSTARTX00026; PROCEDURE: Nine participants were examined within 24 hours of stroke onset and six were re-examined at 1 month post stroke. The examination included administration of an aphasia test, a face recognition task, and a neuroimaging session including T2-, perfusion-, and diffusion-weighted MRI. OUTCOMES #ENTITYSTARTX00026; RESULTS: Participants with a variety of aphasia types and severity were included in the study. Visual inspection suggested larger perfusion abnormality than the actual lesion in eight of nine subjects at day 1. The correlation between aphasia severity and hypoperfusion was significant at day 1 and at 1 month post stroke. However, this was not the case for the relationship between aphasia severity and lesion size where the correlation was not statistically significant at day 1 or at 1 month post stroke. CONCLUSIONS: These results suggest that cerebral hypoperfusion is a more accurate indicator of aphasia severity in early stroke than lesion volume.

Journal Article↗

PubMed2002

Radial fast spin-echo method for T2-weighted imaging and T2 mapping of the liver.

PURPOSE: To evaluate a multishot radial fast-spin echo (RAD-FSE) method developed to improve the quality of abdominal T2-weighted imaging as well as the characterization of focal liver lesions. MATERIALS AND METHODS: The RAD-FSE sequence used in this work consisted of a preparatory period followed by a short echo train (ETL = 16). A novel radial k-space trajectory was used to minimize streaking artifacts due to T2 variations and motion. Small diffusion gradients (b = 1.2 mm/s(2)) were used to improve flow suppression. The quality of images obtained with RAD-FSE was compared to multishot 2DFT fast spin-echo (2DFT-FSE) and half-Fourier acquisition single-shot turbo-spin-echo (HASTE) images using data from 16 patients. A postprocessing algorithm was used to generate multiple high-resolution images (at different effective TE values) as well as a T2 map from a single RAD-FSE data set. The T2 maps were used to differentiate malignant from benign lesions for a set of 33 lesions ranging from 0.8-194 cm(3). RESULTS: RAD-FSE produces high-resolution images of the liver in a breath-hold without the motion artifacts of 2DFT-FSE methods, and without the blurriness and loss of small lesion detectability of HASTE. The inclusion of diffusion weighting in RAD-FSE decreases the signal from blood in hepatic vessels, which improves lesion visualization. The T2 values obtained by postprocessing a single RAD-FSE data set can differentiate malignant from benign lesions. The mean T2 values obtained for malignancies, hemangiomas, and cysts are 108 +/- 30 msec, 240 +/- 14 msec, and 572 +/- 334 msec, respectively. CONCLUSION: These results indicate that RAD-FSE produces abdominal images of higher quality than 2DFT-FSE and HASTE. In addition, lesions can be characterized using T2 maps generated from a single RAD-FSE data set.

Adolescent↗

PubMedDate not supplied

Early response of prostate carcinoma xenografts to docetaxel chemotherapy monitored with diffusion MRI.

For many anticancer therapies, it would be desirable to accurately monitor and quantify tumor response early in the treatment regimen. This would allow oncologists to continue effective therapies or discontinue ineffective therapies early in the course of treatment, and hence, reduce morbidity. This is especially true for second-line therapies, which have reduced response rates and increased toxicities. Previous works by others and ourselves have shown that water mobility, measured by diffusion-weighted magnetic resonance imaging (DW-MRI), increases early in tumors destined to respond to therapies. In the current communication, we further characterize the utility of DW-MRI to predict response of prostate cancer xenografts to docetaxel in SCID mice in a preclinical setting. The current data illustrate that tumor volumes and secreted prostate-specific antigen both respond strongly to docetaxel in a dose-responsive manner, and the apparent diffusion coefficient of water (ADC(w)) increases significantly by 2 days even at the lowest doses (10 mg/kg). The ADCw data were parsed by histogram analyses. Our results indicate that DW-MRI can be used for early detection of prostate carcinoma xenograft response to docetaxel chemotherapy.

Animals↗

PubMedDate not supplied

Changes in water mobility measured by diffusion MRI predict response of metastatic breast cancer to chemotherapy.

The goal of oncology is the individualization of patient care to optimize therapeutic responses and minimize toxicities. Achieving this will require noninvasive, quantifiable, and early markers of tumor response. Preclinical data from xenografted tumors using a variety of antitumor therapies have shown that magnetic resonance imaging (MRI)-measured mobility of tissue water (apparent diffusion coefficient of water, or ADCw) is a biomarker presaging cell death in the tumor. This communication tests the hypothesis that changes in water mobility will quantitatively presage tumor responses in patients with metastatic liver lesions from breast cancer. A total of 13 patients with metastatic breast cancer and 60 measurable liver lesions were monitored by diffusion MRI after initiation of new courses of chemotherapy. MR images were obtained prior to, and at 4, 11, and 39 days following the initiation of therapy for determination of volumes and ADCw values. The data indicate that diffusion MRI can predict response by 4 or 11 days after commencement of therapy, depending on the analytic method. The highest concordance was observed in tumor lesions that were less than 8 cm3 in volume at presentation. These results suggest that diffusion MRI can be useful to predict the response of liver metastases to effective chemotherapy.

Adult↗