Biomedical subjects

Maryann Fitzmaurice

Publications and source records attributed to Maryann Fitzmaurice.

9 recordsLinked to original sources

PubMed2006

Intrinsic fluorescence and diffuse reflectance spectroscopy identify superficial foam cells in coronary plaques prone to erosion.

OBJECTIVE: Foam cells perform critical functions in atherosclerosis. We hypothesize that coronary segments with superficial foam cells (SFCs) situated in a region of interest with a depth of 200 mum can be identified using intrinsic fluorescence spectroscopy (IFS) and diffuse reflectance spectroscopy (DRS). This is a key step in our ongoing program to develop a spectroscopic technique for real-time in vivo diagnosis of vulnerable atherosclerotic plaque. METHODS AND RESULTS: We subjected 132 human coronary segments to in vitro IFS and DRS. We detected SFCs in 13 thick fibrous cap atheromas and 8 pathologic intimal thickening (PIT) lesions. SFCs colocalized with accumulations of smooth muscle cells and proteoglycans, including hyaluronan (P<0.001). Two spectroscopic parameters were generated from analysis of IFS at 480 nm excitation and DRS. A discriminatory algorithm using these parameters identified specimens with SFC area >40%, 20%, 10%, 5%, 2.5%, and 0% of the region of interest with 98%, 98%, 93%, 94%, 93%, and 90% accuracy, respectively. CONCLUSIONS: Our combined IFS and DRS technique accurately detects SFCs in thick fibrous cap atheromas and PIT lesions. Because SFCs are associated with histological markers of plaque erosion, our spectroscopic technique could prove useful in identifying vulnerable plaques.

Algorithms↗

PubMed2006

In vivo margin assessment during partial mastectomy breast surgery using raman spectroscopy.

We present the first demonstration of in vivo collection of Raman spectra of breast tissue. Raman spectroscopy, which analyzes molecular vibrations, is a promising new technique for the diagnosis of breast cancer. We have collected 31 Raman spectra from nine patients undergoing partial mastectomy procedures to show the feasibility of in vivo Raman spectroscopy for intraoperative margin assessment. The data was fit with an established model, resulting in spectral-based tissue characterization in only 1 second. Application of our previously developed diagnostic algorithm resulted in perfect sensitivity and specificity for distinguishing cancerous from normal and benign tissues in our small data set. Significantly, we have detected a grossly invisible cancer that, upon pathologic review, required the patient to undergo a second surgical procedure. Had Raman spectroscopy been used in a real-time fashion to guide tissue excision during the procedure, the additional reexcision surgery might have been avoided. These preliminary findings suggest that Raman spectroscopy has the potential to lessen the need for reexcision surgeries resulting from positive margins and thereby reduce the recurrence rate of breast cancer following partial mastectomy surgeries.

Breast Neoplasms↗

PubMed2005

Diagnosing breast cancer by using Raman spectroscopy.

We employ Raman spectroscopy to diagnose benign and malignant lesions in human breast tissue based on chemical composition. In this study, 130 Raman spectra are acquired from ex vivo samples of human breast tissue (normal, fibrocystic change, fibroadenoma, and infiltrating carcinoma) from 58 patients. Data are fit by using a linear combination model in which nine basis spectra represent the morphologic and chemical features of breast tissue. The resulting fit coefficients provide insight into the chemical/morphological makeup of the tissue and are used to develop diagnostic algorithms. The fit coefficients for fat and collagen are the key parameters in the resulting diagnostic algorithm, which classifies samples according to their specific pathological diagnoses, attaining 94% sensitivity and 96% specificity for distinguishing cancerous tissues from normal and benign tissues. The excellent results demonstrate that Raman spectroscopy has the potential to be applied in vivo to accurately classify breast lesions, thereby reducing the number of excisional breast biopsies that are performed.

Adipose Tissue↗

PubMed2004

Radiofrequency thermal ablation: correlation of hyperacute MR lesion images with tissue response.

PURPOSE: To investigate the hypothesis that the outer boundary of the hyperintense region observed in hyperacute (several minutes post-ablation) T2 and gadolinium contrast-enhanced (CE) T1-weighted magnetic resonance (MR) lesion images is an accurate predictor of eventual cell death from radiofrequency (RF) thermal ablation. MATERIALS AND METHODS: A low-field, open MR imaging system was used to guide an ablation electrode into a thigh muscle of five rabbits and acquire in vivo T2 and CE T1-weighted MR volumes. Ablation occurred by applying RF current for two minutes with the electrode's temperature maintained at 90 degrees +/- 2 degrees C. After fixation, we sliced and photographed the tissue at 3 mm intervals, using a specially designed apparatus, to obtain a volume of tissue images. Digital images of hematoxylin and eosin (H&E) and Masson trichrome-stained histologic samples were obtained, and distinct regions of tissue damage were labeled using a video microscopy system. After the MR and histology images were aligned using a three-dimensional registration method, we compared tissue damage boundaries identified in histology with boundaries marked in MR images. RESULTS: The lesions have distinct zones of tissue damage histologically: a central zone of necrotic cells surrounded by an outer zone with cells that appeared non-viable and associated with marked interstitial edema. In 14 histology images from five lesions, the inner and outer boundaries of the outer zone were compared with the boundaries of a hyperintense rim that surrounds a central hypointense region in the T2 and CE T1-weighted MR images. For T2 and CE T1-weighted MR images, respectively, the mean absolute distance was 1.04 +/- 0.30 mm (mean +/- SD) and 1.00 +/- 0.34 mm for the inner boundaries, and 0.96 +/- 0.34 mm and 0.94 +/- 0.44 mm for the outer boundaries. The mean absolute distances for T2 and CE T1-weighted MR images were not sufficiently different to achieve statistical significance (P = 0.745, 0.818, for the inner and outer boundary, respectively). CONCLUSION: In hyperacute T2 and CE T1-weighted MR lesion images, observations strongly suggest that the outer boundary of the hyperintense rim corresponds to the region of eventual cell necrosis within a distance comparable to our ability to measure. This is good evidence that during RF ablation procedures, MR lesion images can be used to accurately localize the zone of irreversible tissue damage at the lesion margin.

Animals↗

PubMed2003

Radio-frequency-induced thermal lesions: subacute magnetic resonance appearance and histological correlation.

PURPOSE: To investigate the relationship between subacute magnetic resonance (MR) images of radio-frequency (RF) ablation lesions and tissue viability as determined from histological tissue samples. MATERIALS AND METHODS: We generated lesions (N = 5) in a rabbit thigh model. Four days later, we obtained in vivo T(2)- and contrast-enhanced (CE) T(1)-weighted images and ex vivo histological samples approximately perpendicular to the electrode path. Using three-dimensional registration and warping, we spatially compared manually segmented boundaries apparent on MR images to boundaries separating distinct histological zones determined from hematoxylin and eosin (H&E) and Masson trichrome (MT) stains, as well as birefringence studies. RESULTS: Lesions have a characteristic MR appearance: an outer hyperintense margin (M2) separating background tissue (M3) from an inner core (M1), in both T(2) and CE T(1) images. Histologically, there are two zones of damage: an outer zone of likely nonviable cells (H2) separating background tissue (H3) from an inner core of coagulated nonviable cells (H1). We measured distances between automatically computed correspondence points along histological and MR boundaries. For T(2) and CE T(1) images, respectively, M1 vs. H1 distances were 0.72 +/- 0.99 mm (mean +/- SD) and 0.10 +/- 0.95 mm, while outer M2 vs. H2 boundary distances were 0.26 +/- 1.16 mm and 0.05 +/- 1.08 mm. The discrepancy between histological and MR boundaries was larger than the variability in segmenting MR images, but probably within registration error. There were no significant differences between T(2) and CE T(1) boundaries. CONCLUSION: Lesion boundaries apparent in both T(2)- and CE T(1)-weighted MR scans, performed several days postablation, similarly predict the histological response. That is, the lesion core (M1) corresponds to nonviable coagulated cells (H1), while the hyperintense margin (M2) corresponds to likely nonviable cells undergoing necrotic changes (H2).

Animals↗

PubMed2002

Identifying microcalcifications in benign and malignant breast lesions by probing differences in their chemical composition using Raman spectroscopy.

We have applied Raman spectroscopy to analyze the chemical composition of microcalcifications occurring in benign and malignant lesions in the human breast. Microcalcifications were initially separated into two categories based on their Raman spectrum: type I, calcium oxalate dihydrate, and type II, calcium hydroxyapatite. Type I microcalcifications were diagnosed as benign, whereas type II were subdivided into benign and malignant categories using principal component analysis, a statistical technique. Although type II microcalcifications are primarily composed of calcium hydroxyapatite, they also contain trace amounts of several biological impurities. Using principal component analysis, we were able to highlight subtle chemical differences in type II microcalcifications that correlate with breast disease. On the basis of these results, we believe that type II microcalcifications formed in benign ducts typically contain a larger amount of calcium carbonate and a smaller amount of protein than those formed in malignant ducts. Using this diagnostic strategy, we were able to distinguish microcalcifications occurring in benign and malignant ducts with a sensitivity of 88% and a specificity of 93%. This is a significant improvement over current X-ray mammography techniques, which are unable to reliably differentiate microcalcifications in benign and malignant breast lesions.

Adult↗

PubMed2002

Model-based biological Raman spectral imaging.

Raman spectral imaging is a powerful tool for determining chemical information in a biological specimen. The challenge is to condense the large amount of spectral information into an easily visualized form with high information content. Researchers have applied a range of techniques, from peak-height ratios to sophisticated models, to produce interpretable Raman images. The purpose of this article is to review some of the more common imaging approaches, in particular principal components analysis, multivariate curve resolution, and Euclidean distance, as well as to present a new technique, morphological modeling. How to best extract meaningful chemical information using each imaging approach will be discussed and examples of images produced with each will be shown.

Algorithms↗

PubMedDate not supplied

Detection of morphological markers of vulnerable atherosclerotic plaque using multimodal spectroscopy.

Vulnerable plaques, which are responsible for most acute ischemic events, are presently invisible to x-ray angiography. Their primary morphological features include a thin or ulcerated fibrous cap, a large necrotic core, superficial foam cells, and intraplaque hemorrhage. We present evidence that multimodal spectroscopy (MMS), a novel method that combines diffuse reflectance spectroscopy (DRS), intrinsic fluorescence spectroscopy (IFS), and Raman spectroscopy (RS), can detect these markers of plaque vulnerability. To test this concept, we perform an MMS feasibility study on 17 human carotid artery specimens. Following the acquisition of spectra, each specimen is histologically evaluated. Two parameters from DRS, hemoglobin concentration and a scattering parameter, are used to detect intraplaque hemorrhage and foam cells; an IFS parameter that relates to the amount of collagen in the topmost layers of the tissue is used to detect the presence of a thin fibrous cap; and an RS parameter related to the amount of cholesterol and necrotic material is used to detect necrotic core. Taken together, these spectral parameters can generally identify the vulnerable plaques. The results indicate that MMS provides depth-sensitive and complementary morphological information about plaque composition. A prospective in vivo study will be conducted to validate these findings.

Algorithms↗

PubMedDate not supplied

In vivo Raman spectral pathology of human atherosclerosis and vulnerable plaque.

The rupture of vulnerable atherosclerotic plaque accounts for the majority of clinically significant acute cardiovascular events. Because stability of these culprit lesions is directly related to chemical and morphological composition, Raman spectroscopy may be a useful technique for their study. Recent developments in optical fiber probe technology have allowed for the real-time in vivo Raman spectroscopic characterization of human atherosclerotic plaque demonstrated in this work. We spectroscopically examine 74 sites during carotid endarterectomy and femoral artery bypass surgeries. Of these, 34 are surgically biopsied and examined histologically. Excellent signal-to-noise ratio spectra are obtained in only 1 s and fit with an established model, demonstrating accurate tissue characterization. We also report the first evidence that Raman spectroscopy has the potential to identify vulnerable plaque, achieving a sensitivity and specificity of 79 and 85%, respectively. These initial findings indicate that Raman spectroscopy has the potential to be a clinically relevant diagnostic tool for studying cardiovascular disease.

Algorithms↗