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T L Chenevert

Publications and source records attributed to T L Chenevert.

At least 19 recordsLinked to original sources
PubMed2005

Evaluating changes in tumor volume using magnetic resonance imaging during the course of radiotherapy treatment of high-grade gliomas: Implications for conformal dose-escalation studies.

OBJECTIVE: To determine whether changes in tumor volume occur during the course of conformal 3D radiotherapy of high-grade gliomas by use of magnetic resonance imaging (MRI) during treatment and whether these changes had an impact on tumor coverage. METHODS AND MATERIALS: Between December 2000 and January 2004, 21 patients with WHO Grades 3 to 4 supratentorial malignant gliomas treated with 3D conformal radiotherapy (median dose, 70 Gy) were enrolled in a prospective clinical study. All patients underwent T1-weighted contrast-enhancing and T2-weighted and fluid-attenuated inversion recovery (FLAIR) imaging at approximately 1 to 2 weeks before radiotherapy, during radiotherapy (Weeks 1 and 3), and at routine intervals thereafter. All MRI scans were coregistered to the treatment-planning CT. Gross tumor volume (GTV Pre-Rx) was defined from a postoperative T1-weighted contrast-enhancing MRI performed 1 to 2 weeks before start of radiotherapy. A second GTV (GTV Week 3) was defined by use of an MRI performed during Week 3 of radiotherapy. A uniform 0.5 cm expansion of the respective GTV, PTV (Pre-Rx), and PTV (Week 3) was applied to the final boost plan. Dose-volume histograms (DVH) were used to analyze any potential adverse changes in tumor coverage based on Week 3 MRI. RESULTS: All MRI scans were reviewed independently by a neuroradiologist (DGH). Two patients were noted to have multifocal disease at presentation and were excluded from analysis. In 19 cases, changes in the GTV based on MRI at Week 3 during radiotherapy were as follows: 2 cases had an objective decrease in GTV (> or =50%); 12 cases revealed a slight decrease in the rim enhancement or changes in cystic appearance of the GTV; 2 cases showed no change in GTV; and 3 cases demonstrated an increase in tumor volume. Both cases with objective decreases in GTV during treatment were Grade 3 tumors. No cases of tumor progression were noted in Grade 3 tumors during treatment. In comparison, three of 12 Grade 4 tumors had tumor progression, based on MRI obtained during Week 3 of radiotherapy. Median increase in GTV (Week 3) was 11.7 cc (range, 9.8-21.3). Retrospective DVH analysis of PTV (Pre-Rx) and PTV (Week 3) demonstrated a decrease in V(95%)(PTV volume receiving 95% of the prescribed dose) in those 3 cases. CONCLUSIONS: Routine MR imaging during radiotherapy may be essential in ensuring tumor coverage if highly conformal radiotherapy techniques such as stereotactic boost and intensity-modulated radiotherapy are used in dose-escalation trials that utilize smaller treatment margins.

Adult↗
PubMed2004

Diffusion imaging for evaluation of tumor therapies in preclinical animal models.

The increasing development of novel targeted therapies for treating solid tumors has necessitated the development of technology to determine their efficacy in preclinical animal models. One such technology that can non-invasively quantify early changes in tumor cellularity as a result of an efficacious therapy is diffusion MRI. In this overview we present some theories as to the origin of diffusion changes as a result of tumor therapy, a robust methodology for acquisition of apparent diffusion coefficient maps and some applications of determining therapeutic efficacy in a variety therapeutic regimens and animal models.

Animals↗
PubMed2002

Magnetic resonance imaging in cancer research.

Non-invasive assessment of antineoplastic response and correlation of the location, magnitude and duration of transgene expression in vivo would be particularly useful for evaluating cancer gene therapy protocols. This review presents selected examples of how magnetic resonance (MR) has been used to assess therapeutic efficacy by non-invasive quantitation of cell kill, to detect a therapeutic response prior to a change in tumour volume and to detect spatial heterogeneity of the tumour response and quantitate transgene expression. In addition, applications of the use of bioluminescence imaging (BLI) for the evaluation of treatment efficacy and in vivo transgene expression are also presented. These examples provide an overview of areas in which imaging of animal tumour models can contribute towards improving the evaluation of experimental therapeutic agents.

Animals↗
PubMed2001

Multiphase-multistep gadolinium-enhanced MR angiography of the abdominal aorta and runoff vessels.

RATIONALE AND OBJECTIVES: To optimize three-dimensional gadolinium magnetic resonance angiography (3D-Gd-MRA) of the aorta and runoff vessels by addressing fundamentally different requirements for temporal and spatial resolution in a single semiautomated examination. METHODS: The technique was designed to obtain pure arterial-phase 3D-Gd-MR angiograms with adequate spatial resolution for each station while avoiding incomplete enhancement due to delayed filling vessels as well as venous overlay. During gadolinium-chelate infusion, a breath-held multiphase 3D-Gd-MRA scan was initiated in the aorta by automatic triggering, followed by automatic table movement. The acquisition was tailored to the vessels of interest by tilting of the 3D volumes. A spatial resolution of 1.7 x 1.2 x 0.8 mm in the calves was achieved by use of elliptical-centric k-space reordering. Signal-to-noise ratio was maximized with a 12-element peripheral vascular coil. Twelve patients with peripheral vascular disease were studied. RESULTS: In cases of aortic occlusive disease (n = 2), dissections (n = 3), or aneurysms (n = 4), substantially delayed fill-in of reconstituted arteries, false lumens, or aneurysmal segments occurred, which was detected only on the later 3D-Gd-MRA phase. High-resolution arterial-phase scans in the calves were obtained, with only one case of substantial venous overlay. Correlation to digital subtraction angiography revealed excellent agreement of pathological findings. CONCLUSIONS: Multiphase-multistep 3D-Gd-MRA reduces the limitations of standard 3D-Gd-MRA techniques with respect to anatomic coverage, spatial resolution, and nonuniform arterial vessel enhancement.

Adult↗
PubMed2000

Diffusion magnetic resonance imaging: an early surrogate marker of therapeutic efficacy in brain tumors.

BACKGROUND: A surrogate marker for treatment response that can be observed earlier than comparison of sequential magnetic resonance imaging (MRI) scans, which depends on relatively slow changes in tumor volume, may improve survival of brain tumor patients by providing more time for secondary therapeutic interventions. Previous studies in animals with the use of diffusion MRI revealed rapid changes in tumor water diffusion values after successful therapeutic intervention. METHODS: The present study examined the sensitivity of diffusion MRI measurements in orthotopic rat brain tumors derived from implanted rat 9L glioma cells. The effectiveness of therapy for individual brain cancer patients was evaluated by measuring changes in tumor volume on neuroimaging studies conducted 6--8 weeks after the conclusion of a treatment cycle. RESULTS: Diffusion MRI could detect water diffusion changes in orthotopic 9L gliomas after doses of 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU or carmustine) that resulted in as little as 0.2 log cell kill, a measure of tumor cell death. Mean apparent diffusion coefficients in tumors were found to be correlated with and highly sensitive to changes in tumor cellularity (r =.78; two-sided P =.041). The feasibility of serial diffusion MRI in the clinical management of primary brain tumor patients was also demonstrated. Increased diffusion values could be detected in human brain tumors shortly after treatment initiation. The magnitude of the diffusion changes corresponded with clinical outcome. CONCLUSIONS: These results suggest that diffusion MRI will provide an early surrogate marker for quantification of treatment response in patients with brain tumors.

Adolescent↗
PubMed2000

Combined effect of tumor necrosis factor-related apoptosis-inducing ligand and ionizing radiation in breast cancer therapy.

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a potent endogenous activator of the cell death pathway and functions by activating the cell surface death receptors 4 and 5 (DR4 and DR5). TRAIL is nontoxic in vivo and preferentially kills neoplastically transformed cells over normal cells by an undefined mechanism. Radiotherapy is a common treatment for breast cancer as well as many other cancers. Here we demonstrate that ionizing radiation can sensitize breast carcinoma cells to TRAIL-induced apoptosis. This synergistic effect is p53-dependent and may be the result of radiation-induced up-regulation of the TRAIL-receptor DR5. Importantly, TRAIL and ionizing radiation have a synergistic effect in the regression of established breast cancer xenografts. Changes in tumor cellularity and extracellular space were monitored in vivo by diffusion-weighted magnetic resonance imaging (diffusion MRI), a noninvasive technique to produce quantitative images of the apparent mobility of water within a tissue. Increased water mobility was observed in combined TRAIL- and radiation-treated tumors but not in tumors treated with TRAIL or radiation alone. Histological analysis confirmed the loss of cellularity and increased numbers of apoptotic cells in TRAIL- and radiation-treated tumors. Taken together, our results provide support for combining radiation with TRAIL to improve tumor eradication and suggest that efficacy of apoptosis-inducing cancer therapies may be monitored noninvasively, using diffusion MRI.

Animals↗
PubMed2000

Doppler US gating of cardiac MR imaging.

RATIONALE AND OBJECTIVES: Electrocardiographic (ECG) gating of cardiac magnetic resonance (MR) imaging has been problematic for many reasons. The purpose of this study was to demonstrate the feasibility of using Doppler ultrasound (US) gating, either directly off the moving cardiac wall or the systolic upstroke of the arterial signal from the great vessels in neck, in alternative gating modes. MATERIALS AND METHODS: A 2.5-MHz, range-gated Doppler US device was used with A-mode guidance for gating directly off left ventricular wall motion. A 4- or 8.1-MHz, continuous-wave (CW) Doppler US device was used for gating off the systolic upstroke from the great vessels in the neck. The subject undergoing imaging held the transducer against his chest for range-gated Doppler US and against his neck for 8.1-MHz CW Doppler US. The 4-MHz transducer was strapped to the subject's neck. Modified Doppler signals were fed back into the gating circuitry of the MR imager to achieve cardiac synchrony. RESULTS: Cardiac gating was achieved by using both the range-gated technique directly off the cardiac wall and the CW method off blood flow from the great vessels. Problems occurred with radiofrequency shielding during the range-gated method; however, these problems were almost completely removed by use of the CW Doppler probes. CONCLUSION: Doppler US gating of MR images is possible and potentially could overcome many shortcomings of ECG gating. Subsequent embodiments of the technique will require improved radiofrequency shielding in the range-gated technique.

Echocardiography, Doppler↗
PubMed2000

Diffusion MRI detects early events in the response of a glioma model to the yeast cytosine deaminase gene therapy strategy.

Detection of a therapeutic response early in the course of cancer treatment, before tumor growth delay or regression, is not currently possible in experimental models or clinical medicine. New interim measures of therapeutic response would be particularly useful in the development of cancer chemosensitization gene therapy by facilitating optimization of gene transfer protocols and prodrug dosing schedules. Diffusion MRI is a sensitive technique producing quantitative and noninvasive images of the apparent mobility of water within a tissue. We investigated the utility of diffusion MRI for detecting early changes associated with a refined cytosine deaminase (CD)/5-fluorocytosine (5FC) chemosensitization gene therapy paradigm in orthotopic 9L gliomas stably expressing the recently cloned S. cerevisiae CD gene. Mean tumor diffusion increased 31% within 8 days of initiating 5-FC treatment, preceding tumor growth arrest and regression. Complete regression of the intracranial tumor was observed in four of five treated animals, and recurrent tumor in the remaining animal exhibited water diffusion behavior similar to primary, untreated tumors. These results demonstrate the efficacy of the yCD/5FC strategy for glioma and suggest that increased tumor water diffusion is an indicator of active therapeutic intervention.

Animals↗
PubMed2000

Three-dimensional static displacement, stimulated echo NMR elasticity imaging.

This article presents a method for measuring three-dimensional mechanical displacement and strain fields using stimulated echo MRI. Additional gradient pulses encode internal displacements in response to an externally applied deformation. By limiting the mechanical transition to the stimulated echo mixing time, a more accurate static displacement measurement is obtained. A three-dimensional elasticity reconstruction within a region of interest having a uniform shear modulus along its boundary is performed by numerically solving discretized elasticity equilibrium equations. Data acquisition, strain measurements and reconstruction were performed using a silicone gel phantom containing an inclusion of known elastic properties. A comparison between two-dimensional and three-dimensional reconstructions from simulated and experimental displacement data shows higher accuracy from the three-dimensional reconstruction. The long-term objective of this work is to provide a method for remotely palpating and elastically quantitating manually inaccessible tissues.

Echocardiography↗
PubMed2000

Subclavian MR arteriography: reduction of susceptibility artifact with short echo time and dilute gadopentetate dimeglumine.

At arterial phase gadolinium-enhanced magnetic resonance (MR) angiography, artifactual stenosis of the subclavian artery is sometimes seen adjacent to the subclavian vein on the side of the contrast material injection. Experiments in phantoms and in 19 patients showed increased artifact with longer echo time and higher concentration of injected contrast material. An effective method to substantially decrease this susceptibility artifact was threefold dilution of gadopentetate dimeglumine and use of a short echo time (1 msec).

Adolescent↗
PubMed2000

Order information in working memory: fMRI evidence for parietal and prefrontal mechanisms.

Working memory is thought to include a mechanism that allows for the coding of order information. One question of interest is how order information is coded, and how that code is neurally implemented. Here we report both behavioral and fMRI findings from an experiment involved comparing two tasks, an item-memory task and an order-memory task. In each case, five letters were presented for storage, followed after a brief interval by a set of probe letters. In the case of the item-memory task, the two letters were identical, and the subject responded to the question, "Was this letter one of the items you saw?". In the case of the order-memory task, the letters were different, and subjects responded to the question, "Are these two letters in the order in which you saw them?". Behaviorally, items that were further apart in the sequence that elicited faster reaction times and higher accuracy in the Order task. Areas that were significantly more activated in the Order condition included the parietal and prefrontal cortex. Parietal activations overlapped those involved in number processing, leading to the suggestion that the underlying representation of order and numbers may share a common process, coding for magnitude.

Brain Mapping↗
PubMed1999

Motion correction in fMRI via registration of individual slices into an anatomical volume.

An automated retrospective image registration based on mutual information is adapted to a multislice functional magnetic resonance imaging (fMRI) acquisition protocol to provide accurate motion correction. Motion correction is performed by mapping each slice to an anatomic volume data set acquired in the same fMRI session to accommodate inter-slice head motion. Accuracy of the registration parameters was assessed by registration of simulated MR data of the known truth. The widely used rigid body volume registration approach based on stacked slices from the time series data may hinder statistical accuracy by introducing inaccurate assumptions of no motion between slices for multislice fMRI data. Improved sensitivity and specificity of the fMRI signal from mapping-each-slice-to-volume method is demonstrated in comparison with a stacked-slice correction method by examining functional data from two normal volunteers. The data presented in a standard anatomical coordinate system suggest the reliability of the mapping-each-slice-to-volume method to detect the activation signals consistent between the two subjects.

Algorithms↗
PubMed1999

Linear motion correction in three dimensions applied to dynamic gadolinium enhanced breast imaging.

Quantitative analysis of dynamic gadolinium-DTPA (diethylenetriamine pentaacetic acid) enhanced magnetic resonance imaging (MRI) is emerging as a highly sensitive tool for detecting malignant breast tissue. Three-dimensional rapid imaging techniques, such as keyhole MRI, yield high temporal sampling rates to accurately track contrast enhancement and washout in lesions over the course of multiple volume acquisitions. Patient motion during the dynamic acquisitions is a limiting factor that degrades the image quality, particularly of subsequent subtraction images used to identify and quantitatively evaluate regions suggestive of malignancy. Keyhole imaging is particularly sensitive to motion since datasets acquired over an extended period are combined in k-space. In this study, motion is modeled as set of translations in each of the three orthogonal dimensions. The specific objective of the study is to develop and implement an algorithm to correct the consequent phase shifts in k-space data prior to offline keyhole reconstruction three-dimensional (3D) volume breast MR acquisitions.

Algorithms↗
PubMed1998

Contributions of cell kill and posttreatment tumor growth rates to the repopulation of intracerebral 9L tumors after chemotherapy: an MRI study.

The drought of progress in clinical brain tumor therapy provides an impetus for developing new treatments as well as methods for testing therapeutics in animal models. The inability of traditional assays to simultaneously measure tumor size, location, growth kinetics, and cell kill achieved by a treatment complicates the interpretation of therapy experiments in animal models. To address these issues, tumor volume measurements obtained from serial magnetic resonance images were used to noninvasively estimate cell kill values in individual rats with intracerebral 9L tumors after treatment with 0.5, 1, or 2 x LD10 doses of 1,3-bis(2-chloroethyl)-1-nitrosourea. The calculated cell kill values were consistently lower than those reported using traditional assays. A dose-dependent increase in 9L tumor doubling time after treatment was observed that significantly contributed to the time required for surviving cells to repopulate the tumor mass. This study reveals that increases in animal survival are not exclusively attributable to the fraction of tumor cells killed but rather are a function of the cell kill and repopulation kinetics, both of which vary with treatment dose.

Animals↗
PubMed1998

Elasticity reconstructive imaging by means of stimulated echo MRI.

A method is introduced to measure internal mechanical displacement and strain by means of MRI. Such measurements are needed to reconstruct an image of the elastic Young's modulus. A stimulated echo acquisition sequence with additional gradient pulses encodes internal displacements in response to an externally applied differential deformation. The sequence provides an accurate measure of static displacement by limiting the mechanical transitions to the mixing period of the simulated echo. Elasticity reconstruction involves definition of a region of interest having uniform Young's modulus along its boundary and subsequent solution of the discretized elasticity equilibrium equations. Data acquisition and reconstruction were performed on a urethane rubber phantom of known elastic properties and an ex vivo canine kidney phantom using <2% differential deformation. Regional elastic properties are well represented on Young's modulus images. The long-term objective of this work is to provide a means for remote palpation and elasticity quantitation in deep tissues otherwise inaccessible to manual palpation.

Algorithms↗
PubMed1998

Magnetic resonance angiography with gadomer-17. An animal study original investigation.

RATIONALE AND OBJECTIVES: Our purpose was to investigate a "blood pool" contrast agent for abdominal and thoracic MR angiography by comparison with standard ionic and nonionic gadolinium-based contrast agents, which redistribute into the extracellular fluid compartment. METHODS: Abdominal and thoracic MR angiography was performed in three adult dogs using a three-dimensional spoiled gradient echo pulse sequence before and after intravenous administration of one of three gadolinium-based contrast agents (gadopentetate dimeglumine, gadobutrol, and gadomer-17). Each compound was tested at five different doses in all three dogs. Quantitative analysis of signal-to-noise ratio (SNR) was performed in the aorta, inferior vena cava (IVC), liver, spleen, kidney (medulla and cortex), fat, and muscle. RESULTS: Gadomer-17 improved visualization of vascular anatomy at doses of 0.025, 0.05, 0.1, and 0.2 mmol/kg with three-fold greater aorta SNR during the arterial phase and more than four-fold greater aorta and IVC SNR during the equilibrium phase, in comparison with gadopentetate dimeglumine and gadobutrol at equal doses. CONCLUSIONS: Gadomer-17 is a promising contrast agent for both arterial phase and equilibrium phase MR angiography.

Adipose Tissue↗