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Sarah J Nelson

Publications and source records attributed to Sarah J Nelson.

34 records · Page 2Linked to original sources

Measurement of brain glutamate using TE-averaged PRESS at 3T.

A method is introduced that provides improved in vivo spectroscopic measurements of glutamate (Glu), glutamine (Gln), choline (Cho), creatine (Cre), N-acetyl compounds (NAtot, NAA + NAAG), and the inositols (mI and sI). It was found that at 3T, TE averaging, the f1 = 0 slice of a 2D J-resolved spectrum, yielded unobstructed signals for Glu, Glu + Gln (Glx), mI, NA(tot), Cre, and Cho. The C4 protons of Glu at 2.35 ppm, and the C2 protons of Glx at 3.75 ppm were well resolved and yielded reliable measures of Glu/Gln stasis. Apparent T1/T2 values were obtained from the raw data, and metabolite tissue levels were determined relative to a readily available standard. A repeatibility error of <5%, and a coefficient of variation (CV) of <10% were observed for brain Glu levels in a study of six normal volunteers.

Adult↗

Identification of MRI and 1H MRSI parameters that may predict survival for patients with malignant gliomas.

Although MR imaging (MRI) and MR spectroscopic imaging (MRSI) have been applied in the diagnosis and treatment planning for brain tumors, their prognostic significance has not yet been determined. The goal of this study was to identify pre-treatment MRI and MRSI parameters for patients with malignant glioma that may be useful in predicting survival. Two populations of patients with newly-diagnosed malignant glioma were examined with MRI and three-dimensional proton ((1)H) MRSI. Thirty-nine patients (22 grade 3 and 17 glioblastoma multiforme, GBM) were studied prior to surgery, and 33 GBM patients were studied after surgery but prior to treatment with radiation and chemotherapy. Signal intensities of choline (Cho), creatine (Cr), N-acetyl aspartate (NAA), and lactate/lipid (LL) were estimated from the spectra. Recursive partitioning methods were applied to parameters that included age, histological grade, MRI and MRSI variables to generate survival trees. Patients were grouped into high and low risk categories and the corresponding Kaplan-Meier curves were plotted for comparison between groups. The parameters that were selected by recursive partitioning as being predictive of poor outcome were older age, larger contrast enhancement, higher Cho-to-Cr, higher Cho-to-NAA, higher LL and lower Cr-to-NAA abnormalities. The survival functions were significantly different between the sub-groups of patients obtained from the survival tree for both pre-surgery and post-surgery data. The results of this study suggest that pre-treatment MRI and three-dimensional (1)H-MRSI provide information that predicts outcome for patients with malignant gliomas and have drawn attention to variables that should be examined prospectively in future studies using these techniques.

Adult↗

Proton magnetic resonance spectroscopy imaging in the evaluation of patients undergoing gamma knife surgery for Grade IV glioma.

OBJECT: The purpose of this study was to assess the differences in spatial extent and metabolic activity in a comparison of a radiosurgical target defined by conventional strategies that utilize the enhancing lesion and a metabolic lesion defined by proton magnetic resonance spectroscopy (MRS) imaging. The authors evaluated whether these differences manifest themselves in the clinical outcome of patients and assessed the value of incorporating 1H-MRS imaging-derived spatial information into the treatment planning process for gamma knife surgery (GKS). METHODS: Twenty-six patients harboring Grade IV gliomas who had previously been treated with external-beam radiation therapy were evaluated by comparing the radiosurgically treated lesion volume with the volume of metabolically active tumor defined on 1H-MRS imaging. The cohort was evenly divided into two groups based on the percentage of overlap between the radiosurgical target and the metabolic lesion volumes. Patients with a percentage of overlap greater than 50% with respect to the metabolic lesion volume were classified as low risk and those with an overlap less than 50% were classified as high risk. Kaplan-Meier estimators were calculated using time to progression and survival as dependent variables. The metabolite levels within the metabolic lesion were significantly greater than those within the radiosurgical target (p < or = 0.001). The median survival was 15.7 months for patients in the low-risk group and 10.4 months for those in the high-risk group. This difference was statistically significant (p < 0.01). CONCLUSIONS: Analysis of the results of this study indicates that patients undergoing GKS may benefit from the inclusion of 1H-MRS imaging in the treatment planning process.

Adult↗

Challenges in dynamic contrast-enhanced MRI imaging of cervical lymph nodes to detect metastatic disease.

PURPOSE: To identify and overcome challenges in using dynamic contrast-enhanced magnetic resonance imaging (MRI) to distinguish tumor from nontumor in the cervical lymph nodes of patients with squamous cell carcinoma of the head and neck. MATERIALS AND METHODS: Signal-to-noise ratio (S/N), motion, node heterogeneity, and tissue normalizations were examined. Twenty-one patients with squamous cell carcinoma of the head and neck were scanned before a neck dissection (two-dimensional fast spoiled gradient-echo: 10 locations/13 seconds). Peak time, peak enhancement, maximum upslope, and washout slope were measured in pathologically confirmed tumor and nontumor nodes and in the submandibular gland and the sternocleidomastoid muscle. RESULTS: Surface coil arrays provided high coverage and high S/N. Motion averaged 1.1 pixels and was corrected. Large tumor nodes were heterogeneous in their contrast enhancement, while the nontumor nodes were homogeneous. The contrast enhancement parameters were significantly different for all regions except for the submandibular gland compared to the nontumor nodes. CONCLUSION: Challenges of dynamic imaging of cervical lymph nodes were overcome and significant differences were found between the tumor and nontumor nodes, indicating that dynamic imaging is feasible and may aid this patient population.

Analysis of Variance↗

Directional diffusion in relapsing-remitting multiple sclerosis: a possible in vivo signature of Wallerian degeneration.

PURPOSE: To examine the role of directional dependence of the apparent diffusion coefficients in the evaluation of normal-appearing brain regions of patients with relapsing-remitting multiple sclerosis. MATERIALS AND METHODS: The role of diffusion tensor eigenvalues was investigated in the normal-appearing brain regions for 18 patients with relapsing-remitting multiple sclerosis and 15 age-matched normal controls. RESULTS: The isotropic apparent diffusion was increased in all regions. However, reduced anisotropy was significant only in regions with high anisotropy, including the corpus callosum and the internal capsule, and was due to increased diffusion tensor eigenvalues corresponding to diffusion transverse to the fibers without significant increase along the fibers. This characteristic pattern of changes in diffusion tensor eigenvalues has been observed previously in cases of Wallerian degeneration. Low-anisotropy regions corresponded to gray matter and gray/white interface regions. Since fiber tract orientations are not determined for regions of low anisotropy, this characteristic pattern of diffusion change is not detectable in these regions. CONCLUSION: Examination of diffusion tensor eigenvectors may provide insight into the changes observed in diffusion and a signature of Wallerian degeneration in the normal-appearing white matter of relapsing-remitting multiple sclerosis patients.

Adult↗

Assessment of metastatic cervical adenopathy using dynamic contrast-enhanced MR imaging.

BACKGROUND AND PURPOSE: Morphologic assessment by conventional imaging methods of lymph node metastases in patients with squamous cell carcinoma of the head and neck is, at best, insensitive. Doppler sonography has shown that lymph node metastases exhibit alterations in the number of vessels and blood flow. We assessed the ability of dynamic contrast-enhanced MR imaging to differentiate normal from diseased nodes in this patient population. METHODS: Twenty-one patients with newly diagnosed squamous cell carcinoma and no previous treatment were studied with the use of a head and neck phased array surface coil. Anatomic imaging included high resolution T1-weighted, fat-saturated fast spin-echo T2-weighted, and contrast-enhanced T1-weighted imaging (0.99-1.32 mm(3) voxels). The dynamic contrast-enhanced MR imaging was performed by using a 2D fast spoiled gradient recalled sequence with single dose bolus injection of contrast agent. Calculated values included time to peak, peak enhancement, maximum slope, and washout slope for the enhancement. All patients underwent neck dissection as part of their indicated treatment, and imaging results were correlated with pathologic findings. RESULTS: Dynamic contrast-enhanced MR imaging and pathology comparisons were obtained for 68 nodes. There was significantly longer time to peak (P <.001), lower peak enhancement (P <.05), lower maximum slope (P <.01), and slower washout slope (P <.05) in the tumor-involved nodes compared with the normal nodes. CONCLUSION: Analysis of dynamic contrast-enhanced MR imaging can differentiate normal from diseased lymph nodes in patients with squamous cell carcinoma of the head and neck.

Adult↗

Multivoxel magnetic resonance spectroscopy of brain tumors.

Magnetic resonance spectroscopy (MRS) is becoming more widely available for clinical applications and is able to provide information about the metabolic properties of regions of normal and abnormal tissue morphology. A critical question for the clinical management of patients with brain tumors is whether multivoxel MRS is able to add new information to the high-quality anatomical data provided by conventional MR imaging techniques and whether this information is relevant for the diagnosis and clinical management of such patients. In this article, the state of the art for acquiring and analyzing multivoxel MRS data is reviewed and placed in context relative to imaging findings for metastatic and primary brain tumors. The MRS data are seen to provide unique information that when combined with high-quality anatomical MR images has implications for defining tumor type and grade, directing biopsy or surgical resection, planning focal radiation or biological therapies, and understanding the mechanisms of success and failure of new treatments.

Brain Neoplasms↗

Metabolic imaging of low-grade gliomas with three-dimensional magnetic resonance spectroscopy.

PURPOSE: The role of radiotherapy (RT) seems established for patients with low-grade gliomas with poor prognostic factors. Three-dimensional (3D) magnetic resonance spectroscopy imaging (MRSI) has been reported to be of value in defining the extent of glioma infiltration. We performed a study examining the impact MRSI would have on the routine addition of 2-3-cm margins around MRI T2-weighted hyperintensity to generate the treatment planning clinical target volume (CTV) for low-grade gliomas. METHODS AND MATERIALS: Twenty patients with supratentorial gliomas WHO Grade II (7 astrocytomas, 6 oligoastrocytomas, 7 oligodendrogliomas) underwent MRI and MRSI before surgery. The MRI was contoured manually; the regions of interest included T2 hyperintensity and, if present, regions of contrast enhancement on T1-weighted images. The 3D-MRSI peak parameters for choline and N-acetyl-aspartate, acquired voxel-by-voxel, were categorized using a choline/N-acetyl-aspartate index (CNI), a tool for quantitative assessment of tissue metabolite levels, with CNI 2 being the lowest value corresponding to tumor. CNI data were aligned to MRI and displayed as 3D contours. The relationship between the anatomic and metabolic information on tumor extent was assessed by comparing the CNI contours and other MRSI-derived metabolites to the MRI T2 volume. RESULTS: The limitations in the size of the region "excited" meant that MRSI could be used to evaluate only a median 68% of the T2 volume (range 38-100%), leaving the volume T2c. The CNI 2 volume (median 29 cm(3), range 10-73) was contained totally within the T2c in 55% of patients. In the remaining patients, the volume of CNI 2 extending beyond the T2c was quite small (median 2.3 cm(3), range 1.4-5.2), but was not distributed uniformly about the T2c, extending up to 22 mm beyond it. Two patients demonstrated small regions of contrast enhancement corresponding to the regions of highest CNI. Other metabolites, such as creatine and lactate, seem useful for determining less and more radioresistant areas, respectively. CONCLUSION: Metabolically active tumor, as detected by MRSI, is restricted mainly to the T2 hyperintensity in low-grade gliomas, but can extend outside it in a limited and nonuniform fashion up to 2 cm. Therefore, a CTV including T2 and areas of CNI extension beyond the T2 hyperintensity would result in a reduction in the size and a change in the shape of the standard clinical target volumes generated by adding uniform margins of 2-3 cm to the T2 hyperintensity.

Adult↗

Analysis of the spatial characteristics of metabolic abnormalities in newly diagnosed glioma patients.

PURPOSE: To evaluate the role of 3D MR spectroscopic imaging (MRSI) as a tool for characterizing heterogeneity within a lesion in glioma patients. MATERIALS AND METHODS: Forty-nine patients with newly diagnosed glioma were studied with 3D water-suppressed proton (1-H) MRSI. Signal intensities from choline (Cho), creatine (Cr), N-acytel aspartate (NAA), and lactate/lipid (LL) were estimated from the spectra. Regions of interest (ROIs) corresponding to the metabolic abnormalities were defined and compared with the anatomic lesions. RESULTS: This study showed that the tumor burden measured with either the volumes of the metabolic abnormalities or the metabolic levels in the most abnormal voxels was correlated with the degree of malignancy of the tumor. The volumes of elevated Cho and decreased NAA were useful for distinguishing low-grade from high-grade lesions. The volume of abnormal LL was correlated with the existence of necrosis and with the volume of contrast-enhancing lesions in high-grade lesions. The differences in the volume of abnormal LL were also statistically significant between patients in each grade. CONCLUSION: These 3D-MRSI data provide important additional information to conventional MRI for evaluating and characterizing gliomas.

Brain↗

Combined magnetic resonance imaging and spectroscopic imaging approach to molecular imaging of prostate cancer.

Magnetic resonance spectroscopic imaging (MRSI) provides a noninvasive method of detecting small molecular markers (historically the metabolites choline and citrate) within the cytosol and extracellular spaces of the prostate, and is performed in conjunction with high-resolution anatomic imaging. Recent studies in pre-prostatectomy patients have indicated that the metabolic information provided by MRSI combined with the anatomical information provided by MRI can significantly improve the assessment of cancer location and extent within the prostate, extracapsular spread, and cancer aggressiveness. Additionally, pre- and post-therapy studies have demonstrated the potential of MRI/MRSI to provide a direct measure of the presence and spatial extent of prostate cancer after therapy, a measure of the time course of response, and information concerning the mechanism of therapeutic response. In addition to detecting metabolic biomarkers of disease behavior and therapeutic response, MRI/MRSI guidance can improve tissue selection for ex vivo analysis. High-resolution magic angle spinning ((1)H HR-MAS) spectroscopy provides a full chemical analysis of MRI/MRSI-targeted tissues prior to pathologic and immunohistochemical analyses of the same tissue. Preliminary (1)H HR-MAS spectroscopy studies have already identified unique spectral patterns for healthy glandular and stromal tissues and prostate cancer, determined the composition of the composite in vivo choline peak, and identified the polyamine spermine as a new metabolic marker of prostate cancer. The addition of imaging sequences that provide other functional information within the same exam (dynamic contrast uptake imaging and diffusion-weighted imaging) have also demonstrated the potential to further increase the accuracy of prostate cancer detection and characterization.

Humans↗

In vivo molecular imaging for planning radiation therapy of gliomas: an application of 1H MRSI.

Gliomas are infiltrative lesions that typically have poorly defined margins on conventional magnetic resonance (MR) and computed tomography (CT) images. This presents a considerable challenge for planning radiation and other forms of focal therapy, and introduces the possibility of both under-treating macroscopic tumor, and over-treating regions of normal brain tissue. New therapy systems are able to deliver radiation more precisely and accurately to irregular three-dimensional target volumes, and have placed a premium on definition of the spatial extent of the lesion. Proton MR spectroscopic imaging (H-MRSI) has been proposed as an in vivo molecular imaging technique that assists in targeting and predicts response to radiation therapy for patients with gliomas. The evidence that supports the use of H-MRSI for planning radiation treatment is reviewed, together with the technical requirements for implementing data acquisition and analysis procedures in a clinical setting. Although there is room for improvement in the spatial resolution and chemical specificity obtained at the conventional field strength of 1.5 T, there are clear benefits to integrating H-MRSI into treatment planning and follow-up examinations. Further work is required to integrate the results of the H-MRSI examination into the treatment planning workstation, and to improve the quality of the data using more sensitive phased array coils and higher field strength magnets.

Brain Neoplasms↗

Characterization of untreated gliomas by magnetic resonance spectroscopic imaging.

Although there are trends in the morphologic, metabolic, hemodynamic, and structural properties of untreated gliomas that are reflected in MR measurements, there is considerable heterogeneity both within and between lesions of the same histologic grade. The spatial extent of the abnormality in ADC and RA images is similar to the T2 lesion, but there is no obvious difference in intensity between grades. The rCBV is significantly increased in the enhancing volume of grade 4 lesions but is similar or reduced in intensity for most grade 3 lesions. There are clear differences between the enhancing volumes and the regions with increased Cho that may be highly significant for planning focal therapy. The location and intensity of the Lac/Lip peaks are consistent with those representing regions of necrosis for grade 4 lesions. The fact that small Lac/Lip peaks can also be seen in grade 2 and grade 3 lesions suggests that their presence may be indicative of regions that are likely to progress to a higher grade. If this were the case, it would be valuable for directing biopsies. The correlations between rCBV, Cho, and ADC suggest that cellularity, membrane turnover, and vascularity are linked in grade 4 lesions. It is not clear whether there is any relationship between these parameters regions in grade 2 or grade 3 gliomas. While further work is required to optimize the methodology associated with these MR parameters, it seems likely that combining the information from such measurements may be valuable for predicting outcome and tailoring therapy to individual patients.

Brain↗

Histopathological validation of a three-dimensional magnetic resonance spectroscopy index as a predictor of tumor presence.

OBJECT: Data obtained preoperatively from three-dimensional (3D)/proton magnetic resonance (MR) spectroscopy were compared with the results of histopathological assays of tissue biopsies obtained during surgery to verify the sensitivity and specificity of a choline-containing compound-N-acetylaspartate index (CNI) used to distinguish tumor from nontumorous tissue within T2-hyperintense and contrast-enhancing lesions of patients with untreated gliomas. The information gleaned from the biopsy correlation study was used to test the hypothesis that there is metabolically active tumor in nonenhancing regions of the T2-hyperintense lesion that can be detected using MR spectroscopy. METHODS: Patients suspected of harboring a glioma underwent 3D MR spectroscopy during their preoperative MR imaging examination. Surgical navigation techniques were used to record the location of tissue biopsies collected during open resection of the tumor. A receiver operating curve analysis of the CNI and histological characteristics of specimens at each biopsy location was performed to determine the optimal threshold of the CNI required to separate tumor from nontumorous tissue. Histograms of the CNIs within enhancing and nonenhancing regions of lesions appearing on MR images were generated to determine the spatial distribution of CNIs consistent with tumor. CONCLUSIONS: Biopsy samples containing tumor were distinguished from those containing a mixture of normal, edematous, gliotic, and necrotic tissue with 90% sensitivity and 86% specificity by using a CNI threshold of 2.5. The CNIs of nontumorous specimens were significantly different from those of biopsy specimens containing Grade II (p < 0.03), Grade III (p < 0.005), and Grade IV (p < 0.01) tumors. On average, one third to one half of the T2-hyperintense lesion outside the contrast-enhancing lesion contained CNI greater than 2.5.

Aspartic Acid↗

Imaging glioblastoma multiforme.

Glioblastoma multiforme are infiltrative lesions that have a high degree of heterogeneity, both within and between different patients. Imaging is critical for all phases in the evaluation and treatment of these lesions, but has been limited in providing information that is reliable enough to stratify patients into groups with uniform behavior and to predict outcome. Although magnetic resonance imaging is the method of choice for visualizing anatomic features of the lesion, its results are ambiguous in terms of defining the functional characteristics of the lesion and distinguishing tumor from treatment induced necrosis. Recent advances in magnetic resonance have made possible the routine acquisition of physiological data such as perfusion- and diffusion-weighted images and of metabolic data such as water suppressed proton spectroscopic images. These provide quantitative measurements that are more closely related to the biological properties of the tumor and reflect changes in tumor vascularity, cellularity and proliferation that are associated with tumor progression. As the molecular properties that influence invasion and neoplastic transformation are elucidated, it is critical that noninvasive imaging techniques are available for investigating new therapies and tailoring treatment to individual patient characteristics. The data obtained from patients with glioblastoma multiforme have already demonstrated that these new magnetic resonance techniques are able to contribute to diagnosis, characterization of malignant potential, treatment planning and assessment of response to therapy.

Brain Neoplasms↗

Dynamic susceptibility-weighted perfusion imaging of high-grade gliomas: characterization of spatial heterogeneity.

BACKGROUND AND PURPOSE: The advent of new anti-angiogenic therapies has created the need for better defining regions of abnormal vascularity in order to add specificity to the classification of high-grade gliomas. This study investigated MR imaging parameters corresponding to the peak height and percent recovery of the T2* relaxivity curve to characterize angiogenesis and microvascular leakage within the T2 and contrast-enhancing abnormalities in high-grade gliomas. METHODS: Dynamic susceptibility-weighted MR imaging was performed in 41 patients with untreated high-grade glioma during the first pass and recirculation phase of a gadolinium bolus injection. Normalized peak height and percent recovery of the post-bolus signal were calculated on a voxel by voxel basis within the T2 and contrast-enhancing lesions (T2L, CEL) and compared between grade III and grade IV gliomas. RESULTS: Grade IV gliomas showed significantly larger volumes of abnormal peak height and recovery compared to grade III patients (P < .01). Within the CEL, grade IV gliomas exhibited significantly higher peak height values than grade III patients (P < .05). Enhancing grade III patients (n = 7) demonstrated higher minimum values of percent recovery within both regions compared to grade IV patients. Non-enhancing grade III gliomas (n = 11) had significantly elevated minimum percent recovery values when compared to the T2L-CEL region in grade IV patients (n = 23; P < .05). CONCLUSION: Direct measurement of the spatial distribution of tumor microvasculature characteristics has shown considerable heterogeneity within different regions of grade III and grade IV gliomas. Peak height and percent recovery parameters help to improve the specificity for characterization of the degree of angiogenesis and microvascular leakage in these tumors and may be useful in evaluating response to treatment.

Brain Neoplasms↗