Epileptogenesis provoked by prolonged experimental febrile seizures: mechanisms and biomarkers.

Whether long febrile seizures (FSs) can cause epilepsy in the absence of genetic or acquired predisposing factors is unclear. Having established causality between long FSs and limbic epilepsy in an animal model, we studied here if the duration of the inciting FSs influenced the probability of developing subsequent epilepsy and the severity of the spontaneous seizures. We evaluated if interictal epileptifom activity and/or elevation of hippocampal T2 signal on magnetic resonance image (MRI) provided predictive biomarkers for epileptogenesis, and if the inflammatory mediator interleukin-1beta (IL-1beta), an intrinsic element of FS generation, contributed also to subsequent epileptogenesis. We found that febrile status epilepticus, lasting an average of 64 min, increased the severity and duration of subsequent spontaneous seizures compared with FSs averaging 24 min. Interictal activity in rats sustaining febrile status epilepticus was also significantly longer and more robust, and correlated with the presence of hippocampal T2 changes in individual rats. Neither T2 changes nor interictal activity predicted epileptogenesis. Hippocampal levels of IL-1beta were significantly higher for >24 h after prolonged FSs. Chronically, IL-1beta levels were elevated only in rats developing spontaneous limbic seizures after febrile status epilepticus, consistent with a role for this inflammatory mediator in epileptogenesis. Establishing seizure duration as an important determinant in epileptogenesis and defining the predictive roles of interictal activity, MRI, and inflammatory processes are of paramount importance to the clinical understanding of the outcome of FSs, the most common neurological insult in infants and children.

Menstrual cycle-related fluctuations in breast density measured by using three-dimensional MR imaging.

PURPOSE: To investigate the fluctuation of fibroglandular tissue volume (FV) and percentage of breast density (PD) during the menstrual cycle and compare with postmenopausal women by using three-dimensional magnetic resonance (MR)-based segmentation methods. MATERIALS AND METHODS: This study was approved by the Institutional Review Board and was HIPAA compliant. Written informed consent was obtained. Thirty healthy female subjects, 24 premenopausal and six postmenopausal, were recruited. All subjects underwent MR imaging examination each week for 4 consecutive weeks. The breast volume (BV), FV, and PD were measured by two operators to evaluate interoperator variation. The fluctuation of each parameter measured over the course of the four examinations was evaluated on the basis of the coefficient of variation (CV). RESULTS: The results from two operators showed a high Pearson correlation for BV (R(2) = 0.99), FV (R(2) = 0.98), and PD (R(2) = 0.96). The interoperator variation was 3% for BV and around 5%-6% for FV and PD. In the respective premenopausal and postmenopausal groups, the mean CV was 5.0% and 5.6% for BV, 7.6% and 4.2% for FV, and 7.1% and 6.0% for PD. The difference between premenopausal and postmenopausal groups was not significant (all P values > .05). CONCLUSION: The fluctuation of breast density measured at MR imaging during a menstrual cycle was around 7%. The results may help the design and interpretation of future studies by using the change of breast density as a surrogate marker to evaluate the efficacy of hormone-modifying drugs for cancer treatment or cancer prevention.

Breast cancer: evaluation of response to neoadjuvant chemotherapy with 3.0-T MR imaging.

PURPOSE: To assess how the molecular biomarker status of a breast cancer, including human epidermal growth factor receptor 2 (HER2), hormone receptors, and the proliferation marker Ki-67 status, affects the diagnosis at 3.0-T magnetic resonance (MR) imaging. MATERIALS AND METHODS: This study was approved by the institutional review board and was HIPAA compliant. Fifty patients (age range, 28-82 years; mean age, 49 years) receiving neoadjuvant chemotherapy were monitored with 3.0-T MR imaging. The longest dimension of the residual cancer was measured at MR imaging and correlated with pathologic findings. Patients were further divided into subgroups on the basis of HER2, hormone receptor, and Ki-67 status. Pathologic complete response (pCR) was defined as when there were no residual invasive cancer cells. The Pearson correlation was used to correlate MR imaging-determined and pathologic tumor size, and the unpaired t test was used to compare MR imaging-pathologic size discrepancies. RESULTS: Of the 50 women, 14 achieved pCR. There were seven false-negative diagnoses at MR imaging. The overall sensitivity, specificity, and accuracy for diagnosing invasive residual disease at MR imaging were 81%, 93%, and 84%, respectively. The mean MR imaging-pathologic size discrepancy was 0.5 cm ± 0.9 (standard deviation) for HER2-positive cancer and 2.3 cm ± 3.5 for HER2-negative cancer (P = .009). In the HER2-negative group, the size discrepancy was smaller for hormone receptor-negative than for hormone receptor-positive cancers (1.0 cm ± 1.1 vs 3.0 cm ± 4.0, P = .04). The size discrepancy was smaller in patients with 40% or greater Ki-67 expression (0.8 cm ± 1.1) than in patients with 10% or less Ki-67 expression (3.9 cm ± 5.1, P = .06). CONCLUSION: The diagnostic accuracy of breast MR imaging is better in more aggressive than in less aggressive cancers. When MR imaging is used for surgical planning, caution should be taken with HER2-negative hormone receptor-positive cancers.

A new bias field correction method combining N3 and FCM for improved segmentation of breast density on MRI.

PURPOSE: Quantitative breast density is known as a strong risk factor associated with the development of breast cancer. Measurement of breast density based on three-dimensional breast MRI may provide very useful information. One important step for quantitative analysis of breast density on MRI is the correction of field inhomogeneity to allow an accurate segmentation of the fibroglandular tissue (dense tissue). A new bias field correction method by combining the nonparametric nonuniformity normalization (N3) algorithm and fuzzy-C-means (FCM)-based inhomogeneity correction algorithm is developed in this work. METHODS: The analysis is performed on non-fat-sat T1-weighted images acquired using a 1.5 T MRI scanner. A total of 60 breasts from 30 healthy volunteers was analyzed. N3 is known as a robust correction method, but it cannot correct a strong bias field on a large area. FCM-based algorithm can correct the bias field on a large area, but it may change the tissue contrast and affect the segmentation quality. The proposed algorithm applies N3 first, followed by FCM, and then the generated bias field is smoothed using Gaussian kernal and B-spline surface fitting to minimize the problem of mistakenly changed tissue contrast. The segmentation results based on the N3+FCM corrected images were compared to the N3 and FCM alone corrected images and another method, coherent local intensity clustering (CLIC), corrected images. The segmentation quality based on different correction methods were evaluated by a radiologist and ranked. RESULTS: The authors demonstrated that the iterative N3+FCM correction method brightens the signal intensity of fatty tissues and that separates the histogram peaks between the fibroglandular and fatty tissues to allow an accurate segmentation between them. In the first reading session, the radiologist found (N3+FCM > N3 > FCM) ranking in 17 breasts, (N3+FCM > N3 = FCM) ranking in 7 breasts, (N3+FCM = N3 > FCM) in 32 breasts, (N3+FCM = N3 = FCM) in 2 breasts, and (N3 > N3+FCM > FCM) in 2 breasts. The results of the second reading session were similar. The performance in each pairwise Wilcoxon signed-rank test is significant, showing N3+FCM superior to both N3 and FCM, and N3 superior to FCM. The performance of the new N3+FCM algorithm was comparable to that of CLIC, showing equivalent quality in 57/60 breasts. CONCLUSIONS: Choosing an appropriate bias field correction method is a very important preprocessing step to allow an accurate segmentation of fibroglandular tissues based on breast MRI for quantitative measurement of breast density. The proposed algorithm combining N3+FCM and CLIC both yield satisfactory results.

Comparison of breast density measured on MR images acquired using fat-suppressed versus nonfat-suppressed sequences.

PURPOSE: To investigate the difference of MR percent breast density measured from fat-suppressed versus nonfat-suppressed imaging sequences. METHODS: Breast magnetic resonance imaging (MRI) with and without fat suppression was acquired from 38 subjects. Breasts were divided into subgroups of different morphological patterns ("central" and "intermingled" types). Breast volume, fibroglandular tissue volume, and percent density were measured. The results were compared using nonparametric statistical tests and regarded as significant at p < 0.05. RESULTS: Breast volume, fibroglandular volume, and percent density between fat-suppressed and nonfat-suppressed sequences were highly correlated. Breast volumes measured on these two sequences were almost identical. Fibroglandular tissue volume and percent density, however, had small (<5%) yet significant differences between the two sequences-they were both higher on the fat-suppressed sequence. Intraobserver variability was within 4% for both sequences and different morphological types. The fibroglandular tissue volume measured on downsampled images showed a small (<5%) yet significant difference. CONCLUSIONS: The measurement of breast density made on MRI acquired using fat-suppressed and nonfat-suppressed T1W images was about 5% difference, only slightly higher than the intraobserver variability of 3%-4%. When the density data from multiple centers were to be combined, evaluating the degree of difference is needed to take this difference into account.

Decrease in breast density in the contralateral normal breast of patients receiving neoadjuvant chemotherapy: MR imaging evaluation.

PURPOSE: To investigate the change of breast density with quantitative magnetic resonance (MR) imaging in the contralateral normal breast of patients receiving neoadjuvant chemotherapy. MATERIALS AND METHODS: This study was approved by the institutional review board and was HIPAA compliant. Informed consent was obtained. Fifty-four patients with breast cancer (mean age, 47 years; age range, 30-74 years) treated with NAC protocol and enrolled in a breast MR imaging research study were studied. The density in the contralateral normal breast was analyzed by using an MR imaging-based segmentation method. The effect of chemotherapy on the change of density following the doxorubicin and cyclophosphamide (AC) and the AC and taxane regimen was evaluated. The dependence on age was investigated by using a multivariate regression model. RESULTS: In patients who underwent both AC and taxane follow-up, the mean percentage of change from the individual's baseline density was -10% (95% confidence interval: -12.8%, -7.2%) after AC and -12.7% (95% confidence interval: -16%, -9.4%) after AC and taxane. In patients who underwent both follow-up studies after one to two and four cycles of AC, the mean percentage of change was -9.4% (95% confidence interval: -13.5%, -5.3%) after one to two cycles of AC and -14.7% (95% confidence interval: -20.6%, -8.7%) after four cycles of AC. The percentage reduction of density was significantly dependent on age. Patients younger than 40 years had a greater reduction after chemotherapy than patients older than 55 years (P = .01). CONCLUSION: By using three-dimensional MR imaging, patients receiving chemotherapy showed reduction of breast density, and the effects were significant after initial treatment with one to two cycles of the AC regimen.

Quantitative fluorescence tomography using a combined tri-modality FT/DOT/XCT system.

In this work, a first-of-its-kind fully integrated tri-modality system that combines fluorescence, diffuse optical and x-ray tomography (FT/DOT/XCT) into the same setting is presented. The purpose of this system is to perform quantitative fluorescence tomography using multi-modality imaging approach. XCT anatomical information is used as structural priori while optical background heterogeneity information obtained by DOT measurements is used as functional priori. The performance of the hybrid system is evaluated using multi-modality phantoms. In particular, we show that a 2.4 mm diameter fluorescence inclusion located in a heterogeneous medium can be localized accurately with the functional a priori information, although the fluorophore concentration is recovered with 70% error. On the other hand, the fluorophore concentration can be accurately recovered within 8% error only when both DOT optical background functional and XCT structural a priori information are utilized to guide and constrain the FT reconstruction algorithm.

Selection of diagnostic features on breast MRI to differentiate between malignant and benign lesions using computer-aided diagnosis: differences in lesions presenting as mass and non-mass-like enhancement.

PURPOSE: To investigate methods developed for the characterisation of the morphology and enhancement kinetic features of both mass and non-mass lesions, and to determine their diagnostic performance to differentiate between malignant and benign lesions that present as mass versus non-mass types. METHODS: Quantitative analysis of morphological features and enhancement kinetic parameters of breast lesions were used to differentiate among four groups of lesions: 88 malignant (43 mass, 45 non-mass) and 28 benign (19 mass, 9 non-mass). The enhancement kinetics was measured and analysed to obtain transfer constant (K(trans)) and rate constant (k(ep)). For each mass eight shape/margin parameters and 10 enhancement texture features were obtained. For the lesions presenting as nonmass-like enhancement, only the texture parameters were obtained. An artificial neural network (ANN) was used to build the diagnostic model. RESULTS: For lesions presenting as mass, the four selected morphological features could reach an area under the ROC curve (AUC) of 0.87 in differentiating between malignant and benign lesions. The kinetic parameter (k(ep)) analysed from the hot spot of the tumour reached a comparable AUC of 0.88. The combined morphological and kinetic features improved the AUC to 0.93, with a sensitivity of 0.97 and a specificity of 0.80. For lesions presenting as non-mass-like enhancement, four texture features were selected by the ANN and achieved an AUC of 0.76. The kinetic parameter k(ep) from the hot spot only achieved an AUC of 0.59, with a low added diagnostic value. CONCLUSION: The results suggest that the quantitative diagnostic features can be used for developing automated breast CAD (computer-aided diagnosis) for mass lesions to achieve a high diagnostic performance, but more advanced algorithms are needed for diagnosis of lesions presenting as non-mass-like enhancement.

Quantitative analysis of breast parenchymal patterns using 3D fibroglandular tissues segmented based on MRI.

PURPOSE: Mammographic density and breast parenchymal patterns (the relative distribution of fatty and fibroglandular tissue) have been shown to be associated with the risk of developing breast cancer. Percent breast density as determined by mammography is a well-established risk factor, but on the other hand, studies on parenchymal pattern have been scarce, possibly due to the lack of reliable quantitative parameters that can be used to analyze parenchymal tissue distribution. In this study the morphology of fibroglandular tissue distribution was analyzed using three-dimensional breast MRI, which is not subject to the tissue overlapping problem. METHODS: Four parameters, circularity, convexity, irregularity, and compactness, which are sensitive to the shape and margin of segmented fibroglandular tissue, were analyzed for 230 patients. Cases were assigned to one of two distinct parenchymal breast patterns: Intermingled pattern with intermixed fatty and fibroglandular tissue (Type I, N = 141), and central pattern with confined fibroglandular tissue inside surrounded by fatty tissue outside (Type C, N = 89). For each analyzed parameter, the differentiation between these two patterns was analyzed using a two-tailed t-test based on transformed parameters to normal distribution, as well as distribution histograms and ROC analysis. RESULTS: These two groups of patients were well matched both in age (50 +/- 11 vs 50 +/- 11) and in fibroglandular tissue volume (Type I: 104 +/- 62 cm3 vs Type C: 112 +/- 73 cm3). Between Type I and Type C breasts, all four morphological parameters showed significant differences that could be used to differentiate between the two breast types. In the ROC analysis, among all four parameters, the "compactness" could achieve the highest area under the curve of 0.84, and when all four parameters were combined, the AUC could be further increased to 0.94. CONCLUSIONS: The results suggest that these morphological parameters analyzed from 3D MRI can be used to distinguish between intermingled and central dense tissue distribution patterns, and hence may be used to characterize breast parenchymal pattern quantitatively. The availability of these quantitative morphological parameters may facilitate the investigation of the relationship between parenchymal pattern and breast cancer risk.

Impact of skin removal on quantitative measurement of breast density using MRI.

PURPOSE: In breast MRI, skin and fibroglandular tissue commonly possess similar signal intensities, and as such, the inclusion of skin as dense tissue leads to an overestimation in the measured density. This study investigated the impact of skin to the quantitative measurement of breast density using MRI. METHODS: The analysis was performed on the normal breasts of 50 women using nonfat-saturated (nonfat-sat) T1 weighted MR images. The skin was segmented by using a dynamic searching algorithm, which was based on the change in signal intensities from the background air (dark), to the skin (moderate), and then to the fatty tissue (bright). Tissue with moderate intensities that fell between the two boundaries determined based on the intensity gradients (from air to skin, and from skin to fat) was categorized as skin. The percent breast density measured with and without skin exclusion was compared. Also the relationship between the skin volume and the breast volume was investigated. Then, this relationship was used to estimate the skin volume from the breast volume for skin correction. RESULTS: The percentage of the skin volume normalized to the breast volume ranged from 5.0% to 15.2% (median 8.6%, mean +/- STD 8.8 +/- 2.6%) among 50 women. The percent breast densities measured with skin (y) and without skin (x) were highly correlated, y = 1.23x+7% (r = 0.94, p < 0.001). The relationship between the skin volume and the breast volume was analyzed based on transformed data (the square root of the skin volume vs the cube root of breast volume) using the linear regression, and yielded r = 0.87, p < 0.001. When this model was used to estimate the skin volume for correction in the density analysis, it provided a better fit to the measured density with skin exclusion (with adjusted R2 = 0.98, and root mean square error = 1.6) compared to the correction done by using a fixed cutoff value of 8% (adjusted R2 = 0.83, root mean square error = 4.7). CONCLUSIONS: The authors have shown that the skin volume is related to the breast volume, and this relationship may be used to correct for the skin effect in the MRI-based density measurement. A reliable quantitative density analysis method will aid in clinical investigation to evaluate the role of breast density for cancer risk assessment or for prediction of the efficacy of risk-modifying drugs using hormonal therapy.

Age- and race-dependence of the fibroglandular breast density analyzed on 3D MRI.

PURPOSE: The purpose of this study was to evaluate the age- and race-dependence of the breast fibroglandular tissue density based on three-dimensional breast MRI. METHODS: The normal breasts of 321 consecutive patients including Caucasians, Asians, and Hispanics were studied. The subjects were separated into three age groups: Younger than 45, between 45 and 55, and older than 55. Computer algorithms based on body landmarks were used to segment the breast, and fuzzy c-means algorithm was used to segment the fibroglandular tissue. Linear regression analysis was applied to compare mean differences among different age groups and race/ethnicity groups. The obtained parameters were not normally distributed, and the transformed data, natural log (ln) for the fibroglandular tissue volume, and the square root for the percent density were used for statistical analysis. RESULTS: On the average, the transformed fibroglandular tissue volume and percent density decreased significantly with age. Racial differences in mean transformed percent density were found among women older than 45, but not among women younger than 45. Mean percent density was higher in Asians compared to Caucasians and Hispanics; the difference remained significant after adjustment for age, but not significant after adjusted for both age and breast volume. There was no significant difference in the density between the Caucasians and the Hispanics. CONCLUSIONS: The results analyzed using the MRI-based method show age- and race-dependence, which is consistent with literature using mammography-based methods.

Impact of MRI-evaluated neoadjuvant chemotherapy response on change of surgical recommendation in breast cancer.

OBJECTIVE: To investigate how MRI imaging of neoadjuvant chemotherapy (NAC) tumor response affects the recommendation for optimal breast cancer surgery, both before and after NAC. SUMMARY BACKGROUND DATA: Understanding how imaging findings are incorporated into surgeons' decision-making processes will help establish appropriate imaging guidelines for recommending breast conservation surgery (BCS) after the NAC. METHODS: Seventy-six breast cancer patients undergoing NAC with MRI follow-up studies were analyzed. Two experienced breast surgeons reviewed all cases. An initial surgical recommendation was made based on the pre-NAC lesion presentation; a subsequent surgical recommendation was made based on the post-NAC tumor response. Finally, the pathology results were disclosed and the surgeons were asked to decide on the optimal definitive surgical procedure. MRI findings throughout the entire course of the NAC were analyzed to understand how they affected different recommendations. RESULTS: Before the NAC, a large tumor size or extent of disease were the primary determinant factors for mastectomy. In this study, the mean tumor size was 5.3 +/- 3.4 cm (RECIST) in the mastectomy group and 3.2 +/- 1.6 cm in the lumpectomy group (P = 0.0001). After the NAC, based on consensus recommendations, 21 mastectomy candidates remained for mastectomy, with tumor size decreasing from 7.4 +/- 4.5 to 1.5 +/- 2.5 cm, and 22 mastectomy candidates were changed to lumpectomy, with tumor size decreasing from 4.2 +/- 2.1 to 0.4 +/- 0.6 cm. When the final pathology revealed pCR or minimal residual disease, the surgeons agreed that BCS is the optimal procedure. On the other hand, for a large extent of residual disease, mastectomy should be performed. CONCLUSION: In patients who had more extensive pretreatment disease, despite an excellent response to NAC, the surgeons still tended to apply an aggressive approach and recommended mastectomy. Given that the confirmation of pCR or minimal residual disease would change surgeons' recommendations for less aggressive, conservation surgery, the maturity of MRI for NAC response prediction may provide reliable staging information to aid in the recommendation of the optimal surgical procedure.

Predicting pathologic response to neoadjuvant chemotherapy in breast cancer by using MR imaging and quantitative 1H MR spectroscopy.

PURPOSE: To compare changes in the concentration of choline-containing compounds (tCho) and in tumor size at follow-up after neoadjuvant chemotherapy (NAC) between patients who achieved pathologic complete response (pCR) and those who did not (non-pCR). MATERIALS AND METHODS: This study was approved by the institutional review board and was compliant with HIPAA; each patient gave informed consent. Thirty-five patients (mean age, 48 years +/- 11 [standard deviation]; range, 29-75 years) with breast cancer were included. Treatment included doxorubicin and cyclophosphamide followed by a taxane-based regimen. Changes in tCho and tumor size in pCR versus non-pCR groups were compared by using the two-way Mann-Whitney nonparametric test. Receiver operating characteristic (ROC) analysis was performed to differentiate between them and the area under the ROC curve (AUC) was compared. RESULTS: In the pCR group, the tCho level change was greater compared with change in tumor size (P = .003 at first follow-up, P = .01 at second follow-up), but they were not significantly different in the non-pCR group. Changes in tumor size and tCho level at the first follow-up study were not significantly different between the pCR and non-pCR groups but reached significance at the second follow-up. In ROC analysis, the magnetic resonance (MR) imaging and MR spectroscopic parameters had AUCs of 0.65-0.68 at first follow-up; at second follow-up, AUC for change in tumor size was 0.9, AUC for change in tCho was 0.73. CONCLUSION: Patients who show greater reduction in tCho compared with changes in tumor size are more likely to achieve pCR. The change in tumor size halfway through therapy was the most accurate predictor of pCR.

The immune response to herpes simplex virus type 1 infection in susceptible mice is a major cause of central nervous system pathology resulting in fatal encephalitis.

This study was undertaken to investigate possible immune mechanisms in fatal herpes simplex virus type 1 (HSV-1) encephalitis (HSE) after HSV-1 corneal inoculation. Susceptible 129S6 (129) but not resistant C57BL/6 (B6) mice developed intense focal inflammatory brain stem lesions of primarily F4/80(+) macrophages and Gr-1(+) neutrophils detectable by magnetic resonance imaging as early as day 6 postinfection (p.i.). Depletion of macrophages and neutrophils significantly enhanced the survival of infected 129 mice. Immunodeficient B6 (IL-7R(-/-) Kit(w41/w41)) mice lacking adaptive cells (B6-E mice) and transplanted with 129 bone marrow showed significantly accelerated fatal HSE compared to B6-E mice transplanted with B6 marrow or control nontransplanted B6-E mice. In contrast, there was no difference in ocular viral shedding in B6-E mice transplanted with 129 or B6 bone marrow. Acyclovir treatment of 129 mice beginning on day 4 p.i. (24 h after HSV-1 first reaches the brain stem) reduced nervous system viral titers to undetectable levels but did not alter brain stem inflammation or mortality. We conclude that fatal HSE in 129 mice results from widespread damage in the brain stem caused by destructive inflammatory responses initiated early in infection by massive infiltration of innate cells.

Residual breast cancer diagnosed by MRI in patients receiving neoadjuvant chemotherapy with and without bevacizumab.

PURPOSE: To investigate the impact of antiangiogenic therapy with bevacizumab on pathological response and the diagnostic performance of magnetic resonance imaging (MRI) in breast cancer patients. METHODS: Thirty-six patients (aged 31-69 years) with breast cancer were included. Sixteen patients received neoadjuvant chemotherapy (NAC) containing bevacizumab, and 20 patients received the same NAC protocol without bevacizumab. Serial MRI studies were performed to evaluate response. All patients received surgery after completing NAC. The extent of residual disease was examined by histopathology, and classified into three types (pCR-pathologic complete response, confined nodules, and scattered cells). Fisher's exact test and general logistic regression models were applied to analyze differences between two groups. RESULTS: pCR rates and residual disease (nodular and scattered cell) patterns were comparable between the two groups. The diagnostic accuracy rate of MRI (true positive and true negative) was 13/17 (76%) for patients with bevacizumab, and 14/20 (70%) for patients without bevacizumab. The size measured on MRI was accurate for mass lesions that shrank down to nodules, showing <0.7 cm discrepancy from pathological size. For residual disease presenting as scattered cells within a large fibrotic region, MRI could not predict them correctly, resulting in a high false-negative rate and a large size discrepancy. CONCLUSION: The pathological response and the diagnostic performance of MRI are comparable between patients receiving NAC with and without bevacizumab. In both groups MRI has a limitation in detecting residual disease broken down to small foci and scattered cells/clusters. When MRI is used to evaluate the extent of residual disease for surgical treatment, the limitations, particularly for nonmass lesions, should be considered.

Quantitative fluorescence tomography with functional and structural a priori information.

We demonstrate the necessity of functional and structural a priori information for quantitative fluorescence tomography (FT) with phantom studies. Here the functional a priori information is defined as the optical properties of the heterogeneous background that can be measured by a diffuse optical tomography (DOT) system. A CCD-based noncontact hybrid FT/DOT system that could take measurements at multiple views was built. Multimodality phantoms with multiple compartments were constructed and used in the experiments to mimic a heterogeneous optical background. A 3.6 mm diameter object deeply embedded in a heterogeneous optical background could be localized without any a priori information, but the recovered fluorophore concentration only reached one tenth of the true concentration. On the other hand, the true fluorophore concentration could be recovered when both functional and structural a priori information is utilized to guide and constrain the FT reconstruction algorithm.

Simultaneous in vivo dynamic magnetic resonance-diffuse optical tomography for small animal imaging.

We present simultaneous measurement of enhancement kinetics of an optical and a magnetic resonance (MR) contrast agent in a small animal breast tumor model (R3230 ac) using a combined MR-diffuse optical tomographic (MR-DOT) imaging system. A mixture of a small molecular-weight MR contrast agent gadolinium-diethylene-triamine-pentaacetic acid (Gd-DTPA) and a large molecular-weight optical contrast agent indocyanine green (ICG) was administered intravenously for multimodal dynamic imaging. Coregistration of optical and MR images was accomplished using agar-water-based markers. Using T(2) and dynamic T(1) weighted MR images, we divided the entire tumor into two regions of interest (ROI): a viable and a nonviable region. The absorption enhancements in the ROIs were calculated. An enhancement of the ICG was observed in the viable region. On the contrary, there was a lower enhancement in the nonviable region.

Development of a quantitative method for analysis of breast density based on three-dimensional breast MRI.

Breast density has been established as an independent risk factor associated with the development of breast cancer. It is known that an increase of mammographic density is associated with an increased cancer risk. Since a mammogram is a projection image, different body position, level of compression, and the x-ray intensity may lead to a large variability in the density measurement. Breast MRI provides strong soft tissue contrast between fibroglandular and fatty tissues, and three-dimensional coverage of the entire breast, thus making it suitable for density analysis. To develop the MRI-based method, the first task is to achieve consistency in segmentation of the breast region from the body. The method included an initial segmentation based on body landmarks of each individual woman, followed by fuzzy C-mean (FCM) classification to exclude air and lung tissue, B-spline curve fitting to exclude chest wall muscle, and dynamic searching to exclude skin. Then, within the segmented breast, the adaptive FCM was used for simultaneous bias field correction and fibroglandular tissue segmentation. The intraoperator and interoperator reproducibility was evaluated using 11 selected cases covering a broad spectrum of breast densities with different parenchymal patterns. The average standard deviation for breast volume and percent density measurements was in the range of 3%-4% among three trials of one operator or among three different operators. The body position dependence was also investigated by performing scans of two healthy volunteers, each at five different positions, and found the variation in the range of 3%-4%. These initial results suggest that the technique based on three-dimensional MRI can achieve reasonable consistency to be applied in longitudinal follow-up studies to detect small changes. It may also provide a reliable method for evaluating the change of breast density for risk management of women, or for evaluating the benefits/risks when considering hormonal replacement therapy or chemoprevention.

Magnetic resonance imaging features of fibrocystic change of the breast.

PURPOSE: Studies specifically reporting MRI of fibrocystic change (FCC) of the breast are very few and its MRI features are not clearly known. The purpose of this study was to analyze the MRI features of FCC of the breast. MATERIALS AND METHODS: Thirty-one patients with pathologically proven FCC of the breast were retrospectively reviewed. The MRI study was performed using a 1.5-T MR scanner with standard bilateral breast coil. The imaging protocol consisted of pre-contrast T1-weighed imaging and dynamic contrast-enhanced axial T1-weighed imaging. The MRI features were interpreted based on the morphologic and enhancement kinetic descriptors defined on ACR BIRADS-MRI lexicon. RESULTS: FCC of the breast had a wide spectrum of morphologic and kinetic features on MRI. Two types of FCC were found, including a more diffuse type of nonmass lesion (12/31, 39%) showing benign enhancement kinetic pattern with medium wash-in in early phase (9/10, 90%) and a focal mass-type lesion (11/31, 35%) with enhancement kinetic usually showing rapid up-slope mimicking a breast cancer (8/11, 73%). CONCLUSION: MRI is able to elaborate the diverse imaging features of FCC of the breast. Our result showed that FCC presenting as a focal mass-type lesion was usually overdiagnosed as malignancy. Understanding MRI of FCC is important to determine which cohort of patients should be followed up alone or receive aggressive management.

Quantitative correlation between (1)H MRS and dynamic contrast-enhanced MRI of human breast cancer.

Proton magnetic resonance spectroscopy ((1)H MRS) and dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) provide functional information, including vascular volume, vascular permeability and choline (Cho) metabolism. In this study, we applied these two imaging modalities to quantitatively characterize 36 malignant breast lesions in 32 patients and analyzed the correlation between them. Cho concentration was quantified by single-voxel (1)H MRS using water as an internal reference. The measured Cho levels ranged from 0.32 to 10.47 mmol/kg, consistent with previously reported values. In 25 mass-type lesions, the Cho concentration was significantly correlated with tumor size (r=.69, P<.0002). In addition, the Cho level was found to be significantly higher in lesions presenting as mass-type lesions compared to non-mass-type diffuse enhancements (P=.035). The enhancement kinetics from tissues covered within each MRS voxel were measured and analyzed with a two-compartmental model to obtain pharmacokinetic parameters K(trans) and k(ep). A significant correlation was found between the Cho level and the pharmacokinetic parameter k(ep) (r=.62, P<.0001), indicating that tissues with a high Cho level have higher wash-out rates in DCE MRI. The results suggest a correlation between Cho metabolism and angiogenesis activity, which might be explained by the association of Cho with cell replication and angiogenesis required to support tumor growth.