Peter T. Fwu

Diagnostic performance of magnetic resonance imaging for assessing tumor response in patients with HER2-negative breast cancer receiving neoadjuvant chemotherapy is associated with molecular biomarker profile.

BACKGROUND This study aimed to evaluate the influence of hormone receptor (HR) and Ki-67 proliferation markers in predicting the accuracy of magnetic resonance imaging (MRI) for measuring residual tumor size in patients with HER2-negative (HER2(-)) breast cancer receiving neoadjuvant chemotherapy (NAC). PATIENTS AND METHODS Fifty-four women were studied. Patients received AC (doxorubicin (Adriamycin)/cyclophosphamide) and/or taxane-based regimens. The accuracy of MR-determined clinical complete response (CCR) was compared to pathological complete response (pCR). The size of detectable residual tumor on MRI was correlated with pathologically diagnosed tumor size using the Pearson correlation. RESULTS MRI correctly diagnosed 16 of the 17 cases of pCR. There were 8 false-negative diagnoses: 7 HR(+) and 1 HR(-). The overall sensitivity, specificity, and accuracy of MRI were 78%, 94%, and 83%, respectively. The positive predictive value was 97% and the negative predictive value was 67%. For MRI vs. pathologically determined tumor size correlation, HR(-) cancers showed a higher correlation (R = 0.79) than did HR(+) cancers (R = 0.58). A worse MRI/pathology size discrepancy was found in HR(+) cancer than in HR(-)cancer (1.6 ± 2.8 cm vs. 0.56 ± 0.9 cm; P = .05). Tumors with low Ki-67 proliferation (< 40%) showed a larger size discrepancy than did those with high Ki-67 proliferation (≥ 40%) (1.2 ± 2.0 cm vs. 0.4 ± 0.8 cm; P = .05). CONCLUSIONS The results showed that the diagnostic performance of MRI for patients with breast cancer undergoing NAC is associated with a molecular biomarker profile. Among HER2(-)tumors, the accuracy of MRI was worse in HR(+)cancers than in HR(-)cancers and was also worse in low-proliferation tumors than in high-proliferation tumors. These findings may help in surgical planning.

Impact of factors affecting the residual tumor size diagnosed by MRI following neoadjuvant chemotherapy in comparison to pathology

To investigate accuracy of magnetic resonance imaging (MRI) for measuring residual tumor size in breast cancer patients receiving neoadjuvant chemotherapy (NAC).

Nanometer scale imaging by the modulation tracking method

We developed an optical imaging method based on a feedback principle in which the specific scan pattern is adapted according to the shape of the sample. The feedback approach produces nanometer-resolved 3D images of very small and moving features in live cells in seconds. We show images of microvilli in live cultured opossum kidney cells expressing NaPi co-transporter proteins with different GFP constructs and images of cell protrusions in a collagen matrix with a resolution of about 20 nm. We found that in the microvilli the NaPi proteins can be found clustered. Along cell protrusions in 3D we identified cellular adhesions to the extracellular matrix. Our approach to super-resolution and to 3D nanoimaging is different than other proposed methods that break the diffraction limit using non-linear effects or are based on single molecule localization.

Developmental changes in hippocampal shape among preadolescent children

It is known that the largest developmental changes in the hippocampus take place during the prenatal period and during the first two years of postnatal life. Few studies have been conducted to address the normal developmental trajectory of the hippocampus during childhood. In this study shape analysis was applied to study the normal developing hippocampus in a group of 103 typically developing 6‐ to 10‐year‐old preadolescent children. The individual brain was normalized to a template, and then the hippocampus was manually segmented and further divided into the head, body, and tail sub‐regions. Three different methods were applied for hippocampal shape analysis: radial distance mapping, surface‐based template registration using the robust point matching (RPM) algorithm, and volume‐based template registration using the Demons algorithm. All three methods show that the older children have bilateral expanded head segments compared to the younger children. The results analyzed based on radial distance to the centerline were consistent with those analyzed using template‐based registration methods. In analyses stratified by sex, it was found that the age‐associated anatomical changes were similar in boys and girls, but the age‐association was strongest in girls. Total hippocampal volume and sub‐regional volumes analyzed using manual segmentation did not show a significant age‐association. Our results suggest that shape analysis is sensitive to detect sub‐regional differences that are not revealed in volumetric analysis. The three methods presented in this study may be applied in future studies to investigate the normal developmental trajectory of the hippocampus in children. They may be further applied to detect early deviations from the normal developmental trajectory in young children for evaluating susceptibility for psychopathological disorders involving hippocampus.

Consistency of breast density measured from the same women in four different MR scanners

PURPOSE To compare the breast volume (BV), fibroglandular tissue volume (FV), and percent density (PD) measured from breast MRI of the same women using four different MR scanners. METHODS The study was performed in 34 healthy Asian volunteers using two 1.5T (GE and Siemens) and two 3T (GE and Philips) MR scanners. The BV, FV, and PD were measured on nonfat-suppressed T1-weighted images using a comprehensive computer algorithm-based segmentation method. The scanner-to-scanner measurement difference, and the coefficient of variation (CV) among the four scanners were calculated. The measurement variation between two density morphological patterns presenting as the central type and the intermingled type was separately analyzed and compared. RESULTS All four scanners provided satisfactory image quality allowing for successful completion of the segmentation processes. The measured parameters between each pair of MR scanners were highly correlated, with R(2) ≥ 0.95 for BV, R(2) ≥ 0.99 for FV, and R(2) ≥ 0.97 for PD in all comparisons. The mean percent differences between each pair of scanners were 5.9%-7.8% for BV, 5.3%-6.5% for FV, 4.3%-7.3% for PD; with the overall CV of 5.8% for BV, 4.8% for FV, and 4.9% for PD. The variation of FV was smaller in the central type than in the intermingled type (p = 0.04). CONCLUSIONS The results showed that the variation of FV and PD measured from four different MR scanners is around 5%, suggesting the parameters measured using different scanners can be used for a combined analysis in a multicenter study.

Response of bilateral breasts to the endogenous hormonal fluctuation in a menstrual cycle evaluated using 3D MRI

The normal breast tissue responds to the fluctuation of endogenous hormones during a menstrual cycle (MC) and shows changes in breast density. The changes between left and right breasts of the same women were compared to evaluate the symmetrical response. Twenty-four healthy women were recruited in this study. Four weekly magnetic resonance imaging (MRI) studies were performed during one MC. A computer algorithm was used to segment the breast and the fibroglandular tissue to measure the fibroglandular tissue volume (FV) and three morphological parameters: circularity, convexity and irregularity. The coefficient of variation (CV) for each parameter measured among four MRI studies was calculated; also, the maximal percent change between two MRI studies that show the highest and the lowest FV was calculated. These parameters measured from left and right breasts were compared using Pearson correlation. For the FV, the CV measured between left and right breasts of 24 subjects was highly correlated, with r=0.91; the maximal percent difference was also highly correlated, with r=0.93. Overall, the mean left-to-right difference in the measured FV was small: 1.2%±1.1% for CV and 2.6%±2.3% for the maximal percent difference. For the three morphological parameters, the mean left-to-right percentage difference was similar to the differences seen in FV; however, these morphological parameters do not reveal a high functional symmetry between left and right breasts. The results showed that the measured FV from left and right breasts of the same woman revealed a high functional symmetry. Since endogenous hormone plays an important role in the development of breast cancer, it would be interesting to investigate whether the functional asymmetry of response in some patients is associated with the risk of developing unilateral breast cancer.

Quantification of Regional Breast Density in Four Quadrants Using 3D MRI—A Pilot Study

PURPOSE: This study presented a three-dimensional magnetic resonance (MR)–based method to separate a breast into four quadrants for quantitative measurements of the quadrant breast volume (BV) and density. METHODS: Breast MR images from 58 healthy women were studied. The breast and the fibroglandular tissue were segmented by using a computer-based algorithm. A breast was divided into four quadrants using two perpendicular planes intersecting at the nipple or the nipple-centroid line. After the separation, the BV, the fibroglandular tissue volume, and the percent density (PD) were calculated. The symmetry of the quadrant BV in the left and right breasts separated by using the nipple alone, or the nipple-centroid line, was compared. RESULTS: The quadrant separation made on the basis of the nipple-centroid line showed closer BVs in four quadrants than using the nipple alone. The correlation and agreement for the BV in corresponding quadrants of the left and the right breasts were improved after the nipple-centroid reorientation. Among the four quadrants, PD was the highest in the lower outer and the lowest in the upper outer (significant than the other three) quadrants (P < .05). CONCLUSIONS: We presented a quantitative method to divide a breast into four quadrants. The reorientation based on the nipple-centroid line improved the left to right quadrant symmetry, and this may provide a better standardized method to measure quantitative quadrant density. The cancer occurrence rates are known to vary in different sites of a breast, and our method may provide a tool for investigating its association with the quantitative breast density.

Hypothermic Cooling Measured by Thermal Magnetic Resonance Imaging; Feasibility and Implications for Virtual Imaging in the Urogenital Pelvis

OBJECTIVE To study the combination of thermal magnetic resonance imaging (MRI) and novel hypothermic cooling, via an endorectal cooling balloon (ECB), to assess the effective dispersion and temperature drop in pelvic tissue to potentially reduce inflammatory cascade in surgical applications. METHODS Three male subjects, before undergoing robot-assisted radical prostatectomy, were cooled via an ECB, rendered MRI compatible for patient safety before ECB hypothermia. MRI studies were performed using a 3T scanner and included T2-weighted anatomic scan for the pelvic structures, followed by a temperature mapping scan. The sequence was performed repeatedly during the cooling experiment, whereas the phase data were collected using an integrated MR-high-intensity focused ultrasound workstation in real time. Pelvic cooling was instituted with a cooling console located outside the MRI magnet room. RESULTS The feasibility of pelvic cooling measured a temperature drop of the ECB of 20-25 degrees in real time was achieved after an initial time delay of 10-15 seconds for the ECB to cool. The thermal MRI anatomic images of the prostate and neurovascular bundle demonstrate cooling at this interface to be 10-15 degrees, and also that cooling extends into the prostate itself ~5 degrees, and disperses into the pelvic region as well. CONCLUSION An MRI-compatible ECB coupled with thermal MRI is a feasible method to assess effective hypothermic diffusion and saturation to pelvic structures. By inference, hypothermia-induced rectal cooling could potentially reduce inflammation, scarring, and fistula in radical prostatectomy, as well as other urologic tissue procedures of high-intensity focused ultrasound, external beam radiation therapy, radioactive seed implants, transurethral microwave therapy, and transurethral resection of the prostate.

SU‐E‐J‐108: Quantitative Analysis of Longitudinal Cognitive Impairment Due to Radiation Therapy Based on Automatic Segmentation of Hippocampus and Subcortical Structure

PURPOSE In this study, we developed a quantitative analysis tool based on patients longitudinal MR images to 1) measure the radiation dose received by each subcortical structure, 2) follow the change of volume and shape of each structure longitudinally. This tool provides a systematic approach to study the radiation therapy (and subsequent chemotherapy) associated with cognitive impairments. METHODS MRI scans of one patient taken before and after radiation therapy are demonstrated in this study. 3D Conformal radiation therapy was performed on RapidArc™. An open source MRI analysis tool, FMRIBs Integrated Registration and Segmentation Tool (FIRST), was used for segmentation. The images are registered to a standard template with expert-defined labeling for all sub-cortical structures, and the labeling of each structure is mapped back to the individual MRI space for segmentation. After the segmentation, the radiation dose map was coregistered to the MRI space to calculate the dose received by each structure. RESULTS For the structure that is contained within the radiation zone, we can calculate the total dose based on the volumetric distribution of radiation dose. For the structure that is outside the radiation field, we can calculate the distance from the radiation zone. We have demonstrated in this work that the analysis can be done for all segmented sub-cortical structures. The change of volume before and after radiation treatment can be analyzed, and the results can be correlated with the change of cognitive performance over time. CONCLUSIONS We presented an automated tool for efficient, quantitative and user-independent measurements of radiation dose in subcortical structures. The obtained results can be correlated with the cognitive test score and the clinical outcome to evaluate radiation and the subsequent chemotherapy induced changes in brain structures and functions.