Optical imaging correlates with magnetic resonance imaging breast density and reveals composition changes during neoadjuvant chemotherapy

Introduction

In addition to being a risk factor for breast cancer, breast density has been hypothesized to be a surrogate biomarker for predicting response to endocrine-based chemotherapies. The purpose of this study was to evaluate whether a noninvasive bedside scanner based on diffuse optical spectroscopic imaging (DOSI) provides quantitative metrics to measure and track changes in breast tissue composition and density. To access a broad range of densities in a limited patient population, we performed optical measurements on the contralateral normal breast of patients before and during neoadjuvant chemotherapy (NAC). In this work, DOSI parameters, including tissue hemoglobin, water, and lipid concentrations, were obtained and correlated with magnetic resonance imaging (MRI)-measured fibroglandular tissue density. We evaluated how DOSI could be used to assess breast density while gaining new insight into the impact of chemotherapy on breast tissue.

Methods

This was a retrospective study of 28 volunteers undergoing NAC treatment for breast cancer. Both 3.0-T MRI and broadband DOSI (650 to 1,000 nm) were obtained from the contralateral normal breast before and during NAC. Longitudinal DOSI measurements were used to calculate breast tissue concentrations of oxygenated and deoxygenated hemoglobin, water, and lipid. These values were compared with MRI-measured fibroglandular density before and during therapy.

Results

Water (r = 0.843; P < 0.001), deoxyhemoglobin (r = 0.785; P = 0.003), and lipid (r = -0.707; P = 0.010) concentration measured with DOSI correlated strongly with MRI-measured density before therapy. Mean DOSI parameters differed significantly between pre- and postmenopausal subjects at baseline (water, P < 0.001; deoxyhemoglobin, P = 0.024; lipid, P = 0.006). During NAC treatment measured at about 90 days, significant reductions were observed in oxyhemoglobin for pre- (-20.0%; 95% confidence interval (CI), -32.7 to -7.4) and postmenopausal subjects (-20.1%; 95% CI, -31.4 to -8.8), and water concentration for premenopausal subjects (-11.9%; 95% CI, -17.1 to -6.7) compared with baseline. Lipid increased slightly in premenopausal subjects (3.8%; 95% CI, 1.1 to 6.5), and water increased slightly in postmenopausal subjects (4.4%; 95% CI, 0.1 to 8.6). Percentage change in water at the end of therapy compared with baseline correlated strongly with percentage change in MRI-measured density (r = 0.864; P = 0.012).

Conclusions

DOSI functional measurements correlate with MRI fibroglandular density, both before therapy and during NAC. Although from a limited patient dataset, these results suggest that DOSI may provide new functional indices of density based on hemoglobin and water that could be used at the bedside to assess response to therapy and evaluate disease risk.     

Murine MPS I: insights into the pathogenesis of Hurler syndrome

Mucopolysaccharidosis type I (MPS I) is an autosomal recessive disease resulting from deficiency of the lysosomal enzyme α-L-iduronidase. A murine model which shows complete deficiency in α-L-iduronidase activity has been developed and shows phenotypic features similar to severe MPS I in humans. Here we report on the long-term clinical, biochemical, and pathological course of MPS I in mice with emphasis on the skeletal and central nervous system (CNS) manifestations. Affected mice show a progressive clinical course with the development of coarse features, altered growth characteristics and a shortened life span. Progressive lysosomal accumulation is seen in all tissues. Skeletal manifestations represent the earliest clinical finding in MPS I mice with histologic analysis of growth plate and cortical bone revealing evidence that significant early pathology is present. Analysis of the CNS has revealed the novel finding of progressive neuronal loss within the cerebellum. In addition, brain tissue from MPS I mice shows increased levels of GM₂ and GM₃ gangliosides. This murine model clearly shows phenotypic and pathologic features which mimic those seen in severe human MPS I and should be an invaluable tool for the study of the pathogenesis of generalized storage disorders.     

Development of the Adult Scale of Hostility and Aggression: Reactive-Proactive (A-SHARP)

In this study, the authors developed the Adult Scale of Hostility and Aggression Reactive-Proactive (A-SHARP). Sixty-one caregivers rated 512 individuals with intellectual and developmental disabilities on the A-SHARP. Exploratory factor analysis revealed 5 factors on the Problem Scale: (a) Verbal Aggression, (b) Physical Aggression, (c) Hostile Affect, (d) Covert Aggression, and (e) Bullying. Internal consistency was high, and intercorrelation of subscales suggested logical convergent and divergent validity. Separate scores were also derived for the Provocation Scale, which was developed to reflect motivation for the aggression (reactive vs. proactive). Analyses of demographic variables revealed 1 gender effect, several effects due to age and functional level, and no effect of ethnicity. Normative data are provided for the Problem Scale.     

Cooperative behaviour and peer competence in day care and home-reared children

The need for day care in our society has become widespread due to increased numbers of mothers who are entering the work force every year. In recent years, researchers have begun to focus on the care of young children four and under. Some researchers report the years from birth to 3 as having primary importance for social-emotional development (Lichtenberg & Norton, 1972; Banks, 1979; White, 1985). Statistics show that 49.7% of all mothers with infants under one year work outside the home (U.S. Bureau of the Census, 1987), requiring supplemental care for infants. Therefore, the need for day care environments which enhance the social-emotional development of young children is evident. This paper explores the impact of private day care on cooperative behaviour.