Michael Ghijsen, MD, PhD.

All Publications

• Frequent Amplification and Overexpression of PSMA in Basallike Breast Cancer from Analysis of The Cancer Genome Atlas. Journal of nuclear medicine : official publication, Society of Nuclear Medicine Zhou, W., Halder, S., Herwald, S., Ghijsen, M., Shafi, G., Uttarwar, M., Rosen, E., Franc, B., Kishore, S. 2024

  Abstract

  Prostate-specific membrane antigen (PSMA) is frequently overexpressed in nonprostate malignancies. This preclinical study investigated the molecular basis of the application of PMSA-targeting radiopharmaceuticals in breast cancer subtypes. Methods: The somatic copy number status and the transcriptomic and protein expressions of FOLH1 (gene name of PSMA) were analyzed across breast cancer subtypes in 998 patients from The Cancer Genome Atlas dataset. Results: FOLH1 was frequently amplified in basallike breast cancer (BLBC) (32%) compared with luminal and human epidermal growth factor receptor 2-positive subtypes (16% and 17%, respectively; P < 0.01). FOLH1 expression was higher in BLBC (P < 0.001) and was negatively correlated with estrogen-receptor and progesterone-receptor expressions. Consistently, the PSMA protein level was higher in BLBC (P < 0.05). Interestingly, FOLH1 expression was associated with relapse-free and distant metastasis-free survival in patients with BLBC. Conclusion: The BLBC subtype exhibited frequent amplification and overexpression of PSMA, supporting the exploration of PSMA-targeting radiopharmaceuticals in this aggressive breast cancer subtype.

  View details for DOI 10.2967/jnumed.123.266659

  View details for PubMedID 38664014

• Wearable speckle plethysmography (SPG) for characterizing microvascular flow and resistance. Biomedical optics express Ghijsen, M., Rice, T. B., Yang, B., White, S. M., Tromberg, B. J. 2018; 9 (8): 3937-3952

  Abstract

  In this work we introduce a modified form of laser speckle imaging (LSI) referred to as affixed transmission speckle analysis (ATSA) that uses a single coherent light source to probe two physiological signals: one related to pulsatile vascular expansion (classically known as the photoplethysmographic (PPG) waveform) and one related to pulsatile vascular blood flow (named here the speckle plethysmographic (SPG) waveform). The PPG signal is determined by recording intensity fluctuations, and the SPG signal is determined via the LSI dynamic light scattering technique. These two co-registered signals are obtained by transilluminating a single digit (e.g. finger) which produces quasi-periodic waveforms derived from the cardiac cycle. Because PPG and SPG waveforms probe vascular expansion and flow, respectively, in cm-thick tissue, these complementary phenomena are offset in time and have rich dynamic features. We characterize the timing offset and harmonic content of the waveforms in 16 human subjects and demonstrate physiologic relevance for assessing microvascular flow and resistance.

  View details for DOI 10.1364/BOE.9.003937

  View details for PubMedID 30338166

  View details for PubMedCentralID PMC6191642

• Quantitative real-time optical imaging of the tissue metabolic rate of oxygen consumption. Journal of biomedical optics Ghijsen, M., Lentsch, G. R., Gioux, S., Brenner, M., Durkin, A. J., Choi, B., Tromberg, B. J. 2018; 23 (3): 1-12

  Abstract

  The tissue metabolic rate of oxygen consumption (tMRO2) is a clinically relevant marker for a number of pathologies including cancer and arterial occlusive disease. We present and validate a noncontact method for quantitatively mapping tMRO2 over a wide, scalable field of view at 16  frames  /  s. We achieve this by developing a dual-wavelength, near-infrared coherent spatial frequency-domain imaging (cSFDI) system to calculate tissue optical properties (i.e., absorption, μa, and reduced scattering, μs', parameters) as well as the speckle flow index (SFI) at every pixel. Images of tissue oxy- and deoxyhemoglobin concentration (  [  HbO2  ]   and [HHb]) are calculated from optical properties and combined with SFI to calculate tMRO2. We validate the system using a series of yeast-hemoglobin tissue-simulating phantoms and conduct in vivo tests in humans using arterial occlusions that demonstrate sensitivity to tissue metabolic oxygen debt and its repayment. Finally, we image the impact of cyanide exposure and toxicity reversal in an in vivo rabbit model showing clear instances of mitochondrial uncoupling and significantly diminished tMRO2. We conclude that dual-wavelength cSFDI provides rapid, quantitative, wide-field mapping of tMRO2 that can reveal unique spatial and temporal dynamics relevant to tissue pathology and viability.

  View details for DOI 10.1117/1.JBO.23.3.036013

  View details for PubMedID 29575830

  View details for PubMedCentralID PMC5866507

• Real-time simultaneous single snapshot of optical properties and blood flow using coherent spatial frequency domain imaging (cSFDI). Biomedical optics express Ghijsen, M., Choi, B., Durkin, A. J., Gioux, S., Tromberg, B. J. 2016; 7 (3): 870-82

  Abstract

  In this work we present and validate a wide-field method for the real-time mapping of tissue absorption, scattering and blood flow properties over wide regions of tissue (15 cm x 15 cm) with high temporal resolution (50 frames per second). We achieve this by applying Fourier Domain demodulation techniques to coherent spatial frequency domain imaging to extract optical properties and speckle flow index from a single snapshot. Applying this technique to forearm reactive hyperemia protocols demonstrates the ability to resolve intrinsic physiological signals such as the heart beat waveform and the buildup of deoxyhemoglobin associated with oxygen consumption.

  View details for DOI 10.1364/BOE.7.000870

  View details for PubMedID 27231595

  View details for PubMedCentralID PMC4866462

• Optimal analysis method for dynamic contrast-enhanced diffuse optical tomography. International journal of biomedical imaging Ghijsen, M., Lin, Y., Hsing, M., Nalcioglu, O., Gulsen, G. 2011; 2011: 426503

  Abstract

  Diffuse Optical Tomography (DOT) is an optical imaging modality that has various clinical applications. However, the spatial resolution and quantitative accuracy of DOT is poor due to strong photon scatting in biological tissue. Structural a priori information from another high spatial resolution imaging modality such as Magnetic Resonance Imaging (MRI) has been demonstrated to significantly improve DOT accuracy. In addition, a contrast agent can be used to obtain differential absorption images of the lesion by using dynamic contrast enhanced DOT (DCE-DOT). This produces a relative absorption map that consists of subtracting a reconstructed baseline image from reconstructed images in which optical contrast is included. In this study, we investigated and compared different reconstruction methods and analysis approaches for regular endogenous DOT and DCE-DOT with and without MR anatomical a priori information for arbitrarily-shaped objects. Our phantom and animal studies have shown that superior image quality and higher accuracy can be achieved using DCE-DOT together with MR structural a priori information. Hence, implementation of a combined MRI-DOT system to image ICG enhancement can potentially be a promising tool for breast cancer imaging.

  View details for DOI 10.1155/2011/426503

  View details for PubMedID 21811492

  View details for PubMedCentralID PMC3147123