Min-Ying Su

Early clinical PET imaging results with the novel PHF-tau radioligand [F18]-T808.

Aggregates of hyperphosphorylated tau (PHF-tau), such as neurofibrillary tangles, are linked to the degree of cognitive impairment in Alzheimers disease. We have recently reported early clinical results of a novel PHF-tau targeting PET imaging agent, [F18]-T807. Since then, we have investigated a second novel PHF-tau targeting PET imaging agent, [F18]-T808, with different pharmacokinetic characteristics, which may be favorable for imaging Alzheimers disease and other tauopathies. Here, we describe the first human brain images with [F18]-T808.

MRI evaluation of pathologically complete response and residual tumors in breast cancer after neoadjuvant chemotherapy

This study investigated the role of magnetic resonance imaging (MRI) in evaluation of pathologically complete response and residual tumors in patients who were receiving neoadjuvant chemotherapy (NAC) for both positive and negative HER‐2 breast cancer.

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.

Correlation of dynamic contrast enhancement MRI parameters with microvessel density and VEGF for assessment of angiogenesis in breast cancer

To investigate the association between parameters obtained from dynamic contrast enhanced MRI (DCE‐MRI) of breast cancer using different analysis approaches, as well as their correlation with angiogenesis biomarkers (vascular endothelial growth factor and vessel density).

Monitoring the size and response of locally advanced breast cancers to neoadjuvant chemotherapy (weekly paclitaxel and epirubicin) with serial enhanced MRI.

AbstractPurpose. To determine if early cancer size reduction seen on enhanced magnetic resonance imaging (MRI) can serve as a response predictor and to correlate final tumor sizes on MRI and excised gross tumor size to microscopic findings in patients with locally advanced breast cancers treated with preoperative neoadjuvant chemotherapy. Methods and materials. Thirty-three patients with advanced breast cancer entered this prospective chemotherapeutic study. Serial, dynamic, enhanced MRI was performed before chemotherapy induction, after the first course of chemotherapy and after the third course of chemotherapy prior to surgery. Responses were measured by image subtraction of tumor size on subsequent axial MRIs using the response evaluation criteria in solid tumors (RECIST). Early tumor size reduction, percentage of relative early tumor size reduction and final tumor size response were calculated and analyzed statistically. Sizes of residual tumors measured on MRI and gross tumors in excised breasts were correlated with microscopic findings. Results. Based on tumor sizes measured with enhanced MRI, four complete responders (CR), 19 partial responders (PR) and 10 non-responder were documented. Twelve (52%) of the 23 responders (CR and PR) had reached the criteria for PR (≥30% size reduction) after the first course of chemotherapy. All CR had a marked early size reduction (ESR) of more than 45%. Using the receiver operating characteristic (ROC) curve, a good cutoff point for early tumor size reduction was 7.4 cm, with a false positive rate of 0.1 and a false negative rate of 0.13. The percentage of ESR was 8.8%, with a false positive rate of 0.1 and a false negative rate of 0.09. Residual tumor size on MRI correlated well with microscopic findings (r = 0.982, p < 0.001) and gross tumor size in excised breasts correlated moderately with microscopic findings (r = 0.640, p < 0.001). Conclusion. Serial, dynamic, enhanced MRI monitoring of chemotherapeutic response in patients with locally advanced breast cancer can be used to assess early response to chemotherapy and post-chemotherapy tumor size change. Although the residual tumor size on MRI correlated well with the microscopic findings, surgical determination of residual cancer load is still recommended to avoid underestimation.

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.

Frontal Lobe Volume, Function, and β-Amyloid Pathology in a Canine Model of Aging

Application of magnetic resonance imaging (MRI) techniques reveals that human brain aging varies across cortical regions. One area particularly sensitive to normal aging is the frontal lobes. In vitro neuropathological studies and behavioral measures in a canine model of aging previously suggested that the frontal lobes of the dog might be sensitive to aging. In the present study, MRI scans were acquired to compare age-related changes in frontal lobe volume with changes in executive functions andβ-amyloid pathology in the frontal cortex of beagle dogs aged 3 months to 15 years. Decreases in total brain volume appeared only in senior dogs (aged 12 years and older), whereas frontal lobe atrophy developed earlier, appearing in the old dogs (aged 8-11 years). Hippocampal volume also declined with age, but not occipital lobe volume past maturity. Reduced frontal lobe volume correlated with impaired performance on measures of executive function, including inhibitory control and complex working memory, and with increased β-amyloid accumulation in the frontal cortex. Age-related hippocampal atrophy also correlated with complex working memory but not inhibitory control, whereas occipital lobe volume did not correlate with any cognitive measure. These findings are consistent with the frontal lobe theory of aging in humans, which suggests that the frontal lobes and functions subserved by this region are compromised early in aging.

Magnetic resonance imaging of anatomic and vascular characteristics in a canine model of human aging

Dogs exhibit both neuroanatomical and cognitive changes as a function of age that parallel those seen in aging humans. This study describes in vivo changes in neuroanatomical and cerebrovascular characteristics of the canine brain as a function of age in a group of dogs ranging from 4 to 15 years old. Dynamic contrast-enhanced magnetic resonance imaging (MRI) was used to measure the kinetics of contrast agents in the brain. Measures of vascular volume and blood-brain barrier (BBB) permeability were derived from a pharmacokinetic analysis. Cortical atrophy and ventricular enlargement were characteristic features of the aged canine brain. Vascular volume did not vary as a function of age and BBB permeability exhibited a nonsignificant increasing trend with age. However, BBB dysfunction was detected in one middle-aged dog that in addition to having unusually large ventricles, demonstrated an early onset of diffuse senile plaques at postmortem. These findings indicate that BBB dysfunction detected by magnetic resonance imaging may be useful for predicting and potentially diagnosing early pathological conditions.

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

PurposeTo 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. MethodsQuantitative 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 (Ktrans) and rate constant (kep). 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.ResultsFor 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 (kep) 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 kep from the hot spot only achieved an AUC of 0.59, with a low added diagnostic value. ConclusionThe 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.

Significance of Breast Lesion Descriptors in the ACR BI-RADS MRI Lexicon

In recent years, dynamic contrast‐enhanced magnetic resonance imaging (DCE‐MRI) has altered the clinical management for women with breast cancer. In March 2007, the American Cancer Society (ACS) issued a new guideline recommending annual MRI screening for high‐risk women. This guideline is expected to substantially increase the number of women each year who receive breast MRI. The diagnosis of breast MRI involves the description of morphological and enhancement kinetics features. To standardize the communication language, the Breast Imaging Reporting and Data System (BI‐RADS) MRI lexicon was developed by the American College of Radiology (ACR). In this article, the authors will review various appearances of breast lesions on MRI by using the standardized terms of the ACR BI‐RADS MRI lexicon. The purpose is to familiarize all medical professionals with the breast MRI lexicon because the use of this imaging modality is rapidly growing in the field of breast disease. By using this common language, a comprehensive analysis of both morphological and kinetic features used in image interpretation will help radiologists and other clinicians to communicate more clearly and consistently. This may, in turn, help physicians and patients to jointly select an appropriate management protocol for each patients clinical situation. Cancer 2009.