About

The Laboratory of Mathematics in Imaging (LMI) is focused on the application of mathematical theory, analysis, modeling, and signal processing to medical imaging applications. Research projects within the group cover computational and visual display research, and research on novel imaging and treatment methods within the BWH Department of Radiology. Modeling, and the development of novel and efficient technology based on those models, lie at the heart of our research goals. Learn more

Recent Publications

Implementation and Performance of Automated Software for Computing Right-to-Left Ventricular Diameter Ratio From Computed Tomography Pulmonary Angiography Images.

Kumamaru KK, George E, Aghayev A, Saboo SS, Khandelwal A, Rodríguez-López S, Cai T, Jiménez-Carretero D, San José Estépar R, Ledesma-Carbayo MJ, et al. Implementation and Performance of Automated Software for Computing Right-to-Left Ventricular Diameter Ratio From Computed Tomography Pulmonary Angiography Images. J Comput Assist Tomogr. 2016;40 (3) :387-92.Abstract
OBJECTIVE: The aim of this study was to prospectively test the performance and potential for clinical integration of software that automatically calculates the right-to-left ventricular (RV/LV) diameter ratio from computed tomography pulmonary angiography images. METHODS: Using 115 computed tomography pulmonary angiography images that were positive for acute pulmonary embolism, we prospectively evaluated RV/LV ratio measurements that were obtained as follows: (1) completely manual measurement (reference standard), (2) completely automated measurement using the software, and (3 and 4) using a customized software interface that allowed 2 independent radiologists to manually adjust the automatically positioned calipers. RESULTS: Automated measurements underestimated (P < 0.001) the reference standard (1.09 [0.25] vs1.03 [0.35]). With manual correction of the automatically positioned calipers, the mean ratio became closer to the reference standard (1.06 [0.29] by read 1 and 1.07 [0.30] by read 2), and the correlation improved (r = 0.675 to 0.872 and 0.887). The mean time required for manual adjustment (37 [20] seconds) was significantly less than the time required to perform measurements entirely manually (100 [23] seconds). CONCLUSIONS: Automated CT RV/LV diameter ratio software shows promise for integration into the clinical workflow for patients with acute pulmonary embolism.

Lower Pectoralis Muscle Area is Associated with a Worse Overall Survival in Non- Small Cell Lung Cancer.

Kinsey MC, Estepar RSJ, Van der Velden J, Cole BF, Christiani DC, Washko GR. Lower Pectoralis Muscle Area is Associated with a Worse Overall Survival in Non- Small Cell Lung Cancer. Cancer Epidemiol Biomarkers Prev. 2016.Abstract
BACKGROUND: Muscle wasting is a component of the diagnosis of cancer cachexia and has been associated with poor prognosis. However, recommended tools to measure sarcopenia are limited by poor sensitivity or the need to perform additional scans. We hypothesized that pectoralis muscle area (PMA) measured objectively on chest CT scan may be associated with overall survival in non-small cell lung cancer (NSCLC). METHODS: We evaluated two hundred fifty two cases from a prospectively enrolling lung cancer cohort. Eligible cases had CT scans performed prior to the initiation of surgery, radiation, or chemotherapy. PMA was measured in a semi-automated fashion while blinded to characteristics of the tumor, lung, and patient outcomes. RESULTS: Men had a significantly greater PMA than women (37.59 vs 26.19 cm2, P<0.0001). In univariate analysis, PMA was associated with age and BMI. A Cox proportional hazards model was constructed to account for confounders associated with survival. Lower pectoralis area (per cm2) at diagnosis was associated with an increased hazard of death of 2% (HRadj 0.98 [0.96, 0.99], P=0.044) while adjusting for age, sex, smoking, chronic bronchitis, emphysema, histology, stage, chemotherapy, radiation, surgery, BMI, and ECOG performance status. . CONCLUSIONS: Lower pectoralis muscle area measured from chest CT scans obtained at the time of diagnosis of NSCLC is associated with a worse overall survival. IMPACT: Pectoralis muscle area may be a valuable CT biomarker for sarcopenia associated lung cancer survival.

Reorganization of Functional Networks in Verbal Working Memory Circuitry in Early Midlife: The Impact of Sex and Menopausal Status.

Jacobs EG, Weiss B, Makris N, Whitfield-Gabrieli S, Buka SL, Klibanski A, Goldstein JM. Reorganization of Functional Networks in Verbal Working Memory Circuitry in Early Midlife: The Impact of Sex and Menopausal Status. Cereb Cortex. 2016.Abstract
Converging preclinical and human evidence indicates that the decline in ovarian estradiol production during the menopausal transition may play a mechanistic role in the neuronal changes that occur early in the aging process. Here, we present findings from a population-based fMRI study characterizing regional and network-level differences in working memory (WM) circuitry in midlife men and women (N = 142; age range 46-53), as a function of sex and reproductive stage. Reproductive histories and hormonal evaluations were used to determine menopausal status. Participants performed a verbal WM task during fMRI scanning. Results revealed robust differences in task-evoked responses in dorsolateral prefrontal cortex and hippocampus as a function of women's reproductive stage, despite minimal variance in chronological age. Sex differences in regional activity and functional connectivity that were pronounced between men and premenopausal women were diminished for postmenopausal women. Critically, analyzing data without regard to sex or reproductive status obscured group differences in the circuit-level neural strategies associated with successful working memory performance. These findings underscore the importance of reproductive age and hormonal status, over and above chronological age, for understanding sex differences in the aging of memory circuitry. Further, these findings suggest that early changes in working memory circuitry are evident decades before the age range typically targeted in cognitive aging studies.

Myo-inositol changes precede amyloid pathology and relate to APOE genotype in Alzheimer disease.

Voevodskaya O, Sundgren PC, Strandberg O, Zetterberg H, Minthon L, Blennow K, Wahlund L-O, Westman E, Hansson O. Myo-inositol changes precede amyloid pathology and relate to APOE genotype in Alzheimer disease. Neurology. 2016;86 (19) :1754-61.Abstract
OBJECTIVE: We aimed to test whether in vivo levels of magnetic resonance spectroscopy (MRS) metabolites myo-inositol (mI), N-acetylaspartate (NAA), and choline are abnormal already during preclinical Alzheimer disease (AD), relating these changes to amyloid or tau pathology, and functional connectivity. METHODS: In this cross-sectional multicenter study (a subset of the prospective Swedish BioFINDER study), we included 4 groups, representing the different stages of predementia AD: (1) cognitively healthy elderly with normal CSF β-amyloid 42 (Aβ42), (2) cognitively healthy elderly with abnormal CSF Aβ42, (3) patients with subjective cognitive decline and abnormal CSF Aβ42, (4) patients with mild cognitive decline and abnormal CSF Aβ42 (Ntotal = 352). Spectroscopic markers measured in the posterior cingulate/precuneus were considered alongside known disease biomarkers: CSF Aβ42, phosphorylated tau, total tau, [(18)F]-flutemetamol PET, f-MRI, and the genetic risk factor APOE. RESULTS: Amyloid-positive cognitively healthy participants showed a significant increase in mI/creatine and mI/NAA levels compared to amyloid-negative healthy elderly (p < 0.05). In amyloid-positive healthy elderly, mI/creatine and mI/NAA correlated with cortical retention of [(18)F] flutemetamol tracer ([Formula: see text] = 0.44, p = 0.02 and [Formula: see text] = 0.51, p = 0.01, respectively). Healthy elderly APOE ε4 carriers with normal CSF Aβ42 levels had significantly higher mI/creatine levels (p < 0.001) than ε4 noncarriers. Finally, elevated mI/creatine was associated with decreased functional connectivity within the default mode network (rpearson = -0.16, p = 0.02), independently of amyloid pathology. CONCLUSIONS: mI levels are elevated already at asymptomatic stages of AD. Moreover, mI/creatine concentrations were increased in healthy APOE ε4 carriers with normal CSF Aβ42 levels, suggesting that mI levels may reveal regional brain consequences of APOE ε4 before detectable amyloid pathology.

Altered Thalamo-Cortical White Matter Connectivity: Probabilistic Tractography Study in Clinical-High Risk for Psychosis and First-Episode Psychosis.

Cho KIK, Shenton ME, Kubicki M, Jung WH, Lee TY, Yun J-Y, Kim SN, Kwon JS. Altered Thalamo-Cortical White Matter Connectivity: Probabilistic Tractography Study in Clinical-High Risk for Psychosis and First-Episode Psychosis. Schizophr Bull. 2016;42 (3) :723-31.Abstract
Disrupted thalamo-cortical connectivity is regarded as a core psychopathology in patients diagnosed with schizophrenia. However, whether the thalamo-cortical white matter connectivity is disrupted before the onset of psychosis is still unknown. To determine this gap in knowledge, the strength of thalamo-cortical white matter anatomical connectivity in subjects at clinical-high risk for psychosis (CHR) was compared to that of first-episode psychosis (FEP) and healthy controls. A total of 37 CHR, 21 FEP, and 37 matched healthy controls underwent diffusion-weighted magnetic resonance imaging to examine the number of probabilistic tractography "counts" representing thalamo-cortical white matter connectivity. We also investigated the relationship with psychopathology. For FEP, the connectivity between the thalamus and parietal cortex was significantly increased (F= 5.65,P< .05) compared to that of healthy controls. However, the connectivity between thalamus and orbitofrontal cortex was significantly reduced compared to both healthy controls (F= 11.86,P< .005) and CHR (F= 6.63,P< .05). Interestingly, CHR exhibited a similar pattern as FEP, albeit with slightly reduced magnitude. Compared to healthy controls, there was a significant decrease (F= 4.16,P< .05) in CHR thalamo-orbitofrontal connectivity. Also, the strength of the thalamo-orbitofrontal connectivity was correlated with the Global Assessment of Functioning score in CHR (r= .35,P< .05). This observed pattern of white matter connectivity disruptions in FEP and in CHR suggests that this pattern of disconnectivity not only highlights the involvement of thalamus but also might be useful as an early biomarker for psychosis.

Statistical shape analysis using 3D Poisson equation-A quantitatively validated approach.

Gao Y, Bouix S. Statistical shape analysis using 3D Poisson equation-A quantitatively validated approach. Med Image Anal. 2016;30 :72-84.Abstract
Statistical shape analysis has been an important area of research with applications in biology, anatomy, neuroscience, agriculture, paleontology, etc. Unfortunately, the proposed methods are rarely quantitatively evaluated, and as shown in recent studies, when they are evaluated, significant discrepancies exist in their outputs. In this work, we concentrate on the problem of finding the consistent location of deformation between two population of shapes. We propose a new shape analysis algorithm along with a framework to perform a quantitative evaluation of its performance. Specifically, the algorithm constructs a Signed Poisson Map (SPoM) by solving two Poisson equations on the volumetric shapes of arbitrary topology, and statistical analysis is then carried out on the SPoMs. The method is quantitatively evaluated on synthetic shapes and applied on real shape data sets in brain structures.
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