Honors & Awards

  • Stanford Molecular Imaging Scholars Postdoctoral Fellowship, NIH, Stanford University (2014-2016)
  • Milham Fellowship, Dartmouth College (2013)
  • GK-12 Fellowship, NSF (2012-2013)
  • First Place, RIP Conference, Dartmouth College (2011)

Professional Education

  • Doctor of Philosophy, Dartmouth College (2014)
  • Bachelor of Arts, Colorado College (2008)

Stanford Advisors

Research & Scholarship

Current Research and Scholarly Interests

I'm interested in the development of molecular imaging tools through hardware and software for early detection of cancer. Light models can improve photo acoustic image reconstruction to have high quantitative accuracy, leading to more accurate characterization of tumor biology or concentration of imaging agents. A novel acoustic molecular imaging system can be used for deep tissue imaging with non-ionizing radiation and is married to an easily translatable targeted nano-contrast agent.


All Publications

  • MR-Guided Near-Infrared Spectral Tomography Increases Diagnostic Performance of Breast MRI CLINICAL CANCER RESEARCH Mastanduno, M. A., Xu, J., El-Ghussein, F., Jiang, S., Yin, H., Zhao, Y., Wang, K., Ren, F., Gui, J., Pogue, B. W., Paulsen, K. D. 2015; 21 (17): 3906-3912


    The purpose of this study was to determine the diagnostically most important molecular biomarkers quantified by magnetic resonance-guided (MR) near-infrared spectral tomography (NIRST) that distinguish malignant breast lesions from benign abnormalities when combined with outcomes from clinical breast MRI.The study was HIPAA compliant and approved by the Dartmouth Institutional Review Board, the NIH, the United States State Department, and Xijing Hospital. MR-guided NIRST evaluated hemoglobin, water, and lipid content in regions of interest defined by concurrent dynamic contrast-enhanced MRI (DCE-MRI) in the breast. MRI plus NIRST was performed in 44 subjects (median age, 46, age range, 20-81 years), 28 of whom had subsequent malignant pathologic diagnoses, and 16 had benign conditions. A subset of 30 subject examinations yielded optical data that met minimum sensitivity requirements to the suspicious lesion and were included in the analyses of diagnostic performance.In the subset of 30 subject examinations meeting minimum optical data sensitivity criterion, the MR-guided NIRST separated malignant from benign lesions using total hemoglobin (HbT; P < 0.01) and tissue optical index (TOI; P < 0.001). Combined MRI plus TOI data caused one false positive and 1 false negative, and produced the best diagnostic performance, yielding an AUC of 0.95, sensitivity of 95%, specificity of 89%, positive predictive value of 95%, and negative predictive value of 89%, respectively.MRI plus NIRST results correlated well with histopathologic diagnoses and could provide additional information to reduce the number of MRI-directed biopsies.

    View details for DOI 10.1158/1078-0432.CCR-14-2546

    View details for Web of Science ID 000361910000014

    View details for PubMedID 26019171

  • Optimization of image reconstruction for magnetic resonance imaging-guided near-infrared diffuse optical spectroscopy in breast JOURNAL OF BIOMEDICAL OPTICS Zhao, Y., Mastanduno, M. A., Jiang, S., Ei-Ghussein, F., Gui, J., Pogue, B. W., Paulsen, K. D. 2015; 20 (5)


    An optimized approach to nonlinear iterative reconstruction of magnetic resonance imaging (MRI)-guided near-infrared spectral tomography (NIRST) images was developed using an L-curve-based algorithm for the choice of regularization parameter. This approach was applied to clinical exam data to maximize the reconstructed values differentiating malignant and benign lesions. MRI/NIRST data from 25 patients with abnormal breast readings (BI-RADS category 4-5) were analyzed using this optimal regularization methodology, and the results showed enhanced p values and area under the curve (AUC) for the task of differentiating malignant from benign lesions. Of the four absorption parameters and two scatter parameters, the most significant differences for benign versus malignant were total hemoglobin (HbT) and tissue optical index (TOI) with p values = 0.01 and 0.001, and AUC values = 0.79 and 0.94, respectively, in terms of HbT and TOI. This dramatically improved the values relative to fixed regularization (p value = 0.02 and 0.003; AUC = 0.75 and 0.83) showing that more differentiation was possible with the optimal method. Through a combination of both biomarkers, HbT and TOI, the AUC increased from 82.9% (fixed regulation = 0.1) to 94.3% (optimal method).

    View details for DOI 10.1117/1.JBO.20.5.056009

    View details for Web of Science ID 000356241900064

    View details for PubMedID 26000795

  • Sensitivity of MRI-guided near-infrared spectroscopy clinical breast exam data and its impact on diagnostic performance BIOMEDICAL OPTICS EXPRESS Mastanduno, M. A., Xu, J., El-Ghussein, F., Jiang, S., Yin, H., Zhao, Y., Michaelson, K. E., Wang, K., Ren, F., Pogue, B. W., Paulsen, K. D. 2014; 5 (9): 3103-3115


    In this study, data from breast MRI-guided near infrared spectroscopy (NIRS) exams delivered to 44 patients scheduled for surgical resection (ending in 16 benign and 28 malignant diagnoses) were analyzed using a spatial sensitivity metric to quantify the adequacy of the optical measurements for interrogating the tumor region of interest, as derived from the concurrent MRI scan. Along with positional sensitivity, the incorporation of spectral priors and the selection of an appropriate regularization parameter in the image reconstruction were considered, and found to influence the diagnostic accuracy of the recovered images. Once optimized, the MRI/NIRS data was able to differentiate the malignant from benign lesions through both total hemoglobin (p = 0.0037) and tissue optical index (p = 0.00019), but required the relative spatial sensitivity of the optical measurement data to each lesion to be above 1%. Spectral constraints implemented during the reconstruction were required to obtain statistically significant diagnostic information from images of H2O, lipids, and Tissue Optical Index (TOI). These results confirm the need for optical systems that have homogenous spatial coverage of the breast while still being able to accommodate the normal range of breast sizes.

    View details for DOI 10.1364/BOE.5.003103

    View details for Web of Science ID 000341650900021

    View details for PubMedID 25401024

  • Adaptable near-infrared spectroscopy fiber array for improved coupling to different breast sizes during clinical MRI. Academic radiology Mastanduno, M. A., El-Ghussein, F., Jiang, S., DiFlorio-Alexander, R., Junqing, X., Hong, Y., Pogue, B. W., Paulsen, K. D. 2014; 21 (2): 141-150


    Near-infrared spectroscopy (NIRS) of breast can provide functional information on the vascular and structural compartments of tissues in regions identified during simultaneous magnetic resonance imaging (MRI). NIRS can be acquired during dynamic contrast-enhanced MRI (DCE-MRI) to accomplish image-guided spectroscopy of the enhancing regions, potentially increasing the diagnostic specificity of the examination and reducing the number of biopsies performed as a result of inconclusive MRI breast imaging studies.We combine synergistic attributes of concurrent DCE-MRI and NIRS with a new design of the clinical NIRS breast interface that couples to a standard MR breast coil and allows imaging of variable breast sizes. Spectral information from healthy volunteers and cancer patients is recovered, providing molecular information in regions defined by the segmented MR image volume.The new coupling system significantly improves examination utility by allowing improved coupling of the NIR fibers to breasts of all cup sizes and lesion locations. This improvement is demonstrated over a range of breast sizes (cup size A through D) and normal tissue heterogeneity using a group of eight healthy volunteers and two cancer patients. Lesions located in the axillary region and medial-posterior breast are now accessible to NIRS optodes. Reconstructed images were found to have biologically plausible hemoglobin content, oxygen saturation, and water and lipid fractions.In summary, a new NIRS/MRI breast interface was developed to accommodate the variation in breast sizes and lesion locations that can be expected in clinical practice. DCE-MRI-guided NIRS quantifies total hemoglobin, oxygenation, and scattering in MR-enhancing regions, increasing the diagnostic information acquired from MR examinations.

    View details for DOI 10.1016/j.acra.2013.09.025

    View details for PubMedID 24439327

  • Hybrid photomultiplier tube and photodiode parallel detection array for wideband optical spectroscopy of the breast guided by magnetic resonance imaging JOURNAL OF BIOMEDICAL OPTICS El-Ghussein, F., Mastanduno, M. A., Jiang, S., Pogue, B. W., Paulsen, K. D. 2014; 19 (1)


    A new optical parallel detection system of hybrid frequency and continuous-wave domains was developed to improve the data quality and accuracy in recovery of all breast optical properties. This new system was deployed in a previously existing system for magnetic resonance imaging (MRI)-guided spectroscopy, and allows incorporation of additional near-infrared wavelengths beyond 850 nm, with interlaced channels of photomultiplier tubes (PMTs) and silicon photodiodes (PDs). The acquisition time for obtaining frequency-domain data at six wavelengths (660, 735, 785, 808, 826, and 849 nm) and continuous-wave data at three wavelengths (903, 912, and 948 nm) is 12 min. The dynamic ranges of the detected signal are 105 and 106 for PMT and PD detectors, respectively. Compared to the previous detection system, the SNR ratio of frequency-domain detection was improved by nearly 103 through the addition of an RF amplifier and the utilization of programmable gain. The current system is being utilized in a clinical trial imaging suspected breast cancer tumors as detected by contrast MRI scans.

    View details for DOI 10.1117/1.JBO.19.1.011010

    View details for Web of Science ID 000331892700011

    View details for PubMedID 23979460

  • Automatic and robust calibration of optical detector arrays for biomedical diffuse optical spectroscopy BIOMEDICAL OPTICS EXPRESS Mastanduno, M. A., Jiang, S., DiFlorio-Alexander, R., Pogue, B. W., Paulsen, K. D. 2012; 3 (10): 2339-2352


    The design and testing of a new, fully automated, calibration approach is described. The process was used to calibrate an image-guided diffuse optical spectroscopy system with 16 photomultiplier tubes (PMTs), but can be extended to any large array of optical detectors and associated imaging geometry. The design goals were accomplished by developing a routine for robust automated calibration of the multi-detector array within 45 minutes. Our process was able to characterize individual detectors to a median norm of the residuals of 0.03 V for amplitude and 4.4 degrees in phase and achieved less than 5% variation between all the detectors at the 95% confidence interval for equivalent measurements. Repeatability of the calibrated data from the imaging system was found to be within 0.05 V for amplitude and 0.2 degrees for phase, and was used to evaluate tissue-simulating phantoms in two separate imaging geometries. Spectroscopic imaging of total hemoglobin concentration was recovered to within 5% of the true value in both cases. Future work will focus on streamlining the technology for use in a clinical setting with expectations of achieving accurate quantification of suspicious lesions in the breast.

    View details for Web of Science ID 000309557700001

    View details for PubMedID 23082277

  • Remote positioning optical breast magnetic resonance coil for slice-selection during image-guided near-infrared spectroscopy of breast cancer JOURNAL OF BIOMEDICAL OPTICS Mastanduno, M. A., Jiang, S., DiFlorio-Alexander, R., Pogue, B. W., Paulsen, K. D. 2011; 16 (6)


    The design and testing of a pneumatic optical positioning interface produced with the goal of improving fiber positioning in magnetic resonance (MR)-guided diffuse spectral imaging of breast cancer is presented. The system was created for vertical positioning of optical fibers inside the MR bore during a patient exam to target suspicious lesions with MR scans for reference and collect multiple planes of optical data. The interface includes new fiber plates for mechanical and optical coupling to the breast, and was tested in phantoms and human imaging. Reconstructions with data taken in the new interface show acceptable linearity over different absorber concentrations (residual norm = 0.067), and exhibit good contrast recovery at different imaging planes, which is consistent with previous work. An example of human breast imaging through the new interface is shown and a discussion of how it compares to other patient interfaces for breast imaging is presented. Design goals of increasing the available degrees of freedom for fiber positioning while maintaining good patient-fiber contact and comfort were accomplished. This interface allows improved volumetric imaging with interactive and accurate slice selection to quantify targeted suspicious lesions.

    View details for DOI 10.1117/1.3587631

    View details for Web of Science ID 000293086800007

    View details for PubMedID 21721802

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