NIR Fluorescent Imaging and Photodynamic Therapy with a Novel Theranostic Phospholipid Probe for Triple-Negative Breast Cancer Cells.

New exogenous probes are needed for both imaging diagnostics and therapeutics. Here, we introduce a novel nanocomposite near-infrared (NIR) fluorescent imaging probe and test its potency as a photosensitizing agent for photodynamic therapy (PDT) against triple-negative breast cancer cells. The active component in the nanocomposite is a small molecule, pyropheophorbide a-phosphatidylethanolamine-QSY21 (Pyro-PtdEtn-QSY), which is imbedded into lipid nanoparticles for transport in the body. The probe targets abnormal choline metabolism in cancer cells; specifically, the overexpression of phosphatidylcholine-specific phospholipase C (PC-PLC) in breast, prostate, and ovarian cancers. Pyro-PtdEtn-QSY consists of a NIR fluorophore and a quencher, attached to a PtdEtn moiety. It is selectively activated by PC-PLC resulting in enhanced fluorescence in cancer cells compared to normal cells. In our in vitro investigation, four breast cancer cell lines showed higher probe activation levels than noncancerous control cells, immortalized human mammary gland cells, and normal human T cells. Moreover, the ability of this nanocomposite to function as a sensitizer in PDT experiments on MDA-MB-231 cells suggests that the probe is promising as a theranostic agent.

Breast cancer differential diagnosis using diffuse optical spectroscopic imaging and regression with z-score normalized data.

SIGNIFICANCE: Current imaging paradigms for differential diagnosis of suspicious breast lesions suffer from high false positive rates that force patients to undergo unnecessary biopsies. Diffuse optical spectroscopic imaging (DOSI) noninvasively probes functional hemodynamic and compositional parameters in deep tissue and has been shown to be sensitive to contrast between normal and malignant tissues. AIM: DOSI methods are under investigation as an adjunct to mammography and ultrasound that could reduce false positive rates and unnecessary biopsies, particularly in radiographically dense breasts. METHODS: We performed a retrospective analysis of 212 subjects with suspicious breast lesions who underwent DOSI imaging. Physiological tissue parameters were z-score normalized to the patient's contralateral breast tissue and input to univariate logistic regression models to discriminate between malignant tumors and the surrounding normal tissue. The models were then used to differentiate malignant lesions from benign lesions. RESULTS: Models incorporating several individual hemodynamic parameters were able to accurately distinguish malignant tumors from both the surrounding background tissue and benign lesions with area under the curve (AUC) ≥0.85. Z-score normalization improved the discriminatory ability and calibration of these predictive models relative to unnormalized or ratio-normalized data. CONCLUSIONS: Findings from a large subject population study show how DOSI data normalization that accounts for normal tissue heterogeneity and quantitative statistical regression approaches can be combined to improve the ability of DOSI to diagnose malignant lesions. This improved diagnostic accuracy, combined with the modality's inherent logistical advantages of portability, low cost, and nonionizing radiation, could position DOSI as an effective adjunct modality that could be used to reduce the number of unnecessary invasive biopsies.

Hybrid time-domain and continuous-wave diffuse optical tomography instrument with concurrent, clinical magnetic resonance imaging for breast cancer imaging.

Diffuse optical tomography has demonstrated significant potential for clinical utility in the diagnosis and prognosis of breast cancer, and its use in combination with other structural imaging modalities improves lesion localization and the quantification of functional tissue properties. Here, we introduce a hybrid diffuse optical imaging system that operates concurrently with magnetic resonance imaging (MRI) in the imaging suite, utilizing commercially available MR surface coils. The instrument acquires both continuous-wave and time-domain diffuse optical data in the parallel-plate geometry, permitting both absolute assignment of tissue optical properties and three-dimensional tomography; moreover, the instrument is designed to incorporate diffuse correlation spectroscopic measurements for probing tissue blood flow. The instrument is described in detail here. Image reconstructions of a tissue phantom are presented as an initial indicator of the system's ability to accurately reconstruct optical properties and the concrete benefits of the spatial constraints provided by concurrent MRI. Last, we briefly discuss how various data combinations that the instrument could facilitate, including tissue perfusion, can enable more comprehensive assessment of lesion physiology.

Tissue oxygen saturation predicts response to breast cancer neoadjuvant chemotherapy within 10 days of treatment.

Ideally, neoadjuvant chemotherapy (NAC) assessment should predict pathologic complete response (pCR), a surrogate clinical endpoint for 5-year survival, as early as possible during typical 3- to 6-month breast cancer treatments. We introduce and demonstrate an approach for predicting pCR within 10 days of initiating NAC. The method uses a bedside diffuse optical spectroscopic imaging (DOSI) technology and logistic regression modeling. Tumor and normal tissue physiological properties were measured longitudinally throughout the course of NAC in 33 patients enrolled in the American College of Radiology Imaging Network multicenter breast cancer DOSI trial (ACRIN-6691). An image analysis scheme, employing z-score normalization to healthy tissue, produced models with robust predictions. Notably, logistic regression based on z-score normalization using only tissue oxygen saturation (StO2) measured within 10 days of the initial therapy dose was found to be a significant predictor of pCR (AUC = 0.92; 95% CI: 0.82 to 1). This observation suggests that patients who show rapid convergence of tumor tissue StO2 to surrounding tissue StO2 are more likely to achieve pCR. This early predictor of pCR occurs prior to reductions in tumor size and could enable dynamic feedback for optimization of chemotherapy strategies in breast cancer.

Relationship between hypothermia and blood loss in adult patients undergoing open lumbar spine surgery.

CONTEXT: Intraoperative blood loss during open lumbar spine surgery is associated with adverse events and is a contributor to higher medical costs. Intraoperative hypothermia has been shown to increase blood loss and postoperative allogeneic blood transfusion rates in other realms of orthopedic surgery, but it has not been studied extensively in patients undergoing spine surgery. OBJECTIVE: To determine whether a clinically relevant association exists between intraoperative core body temperature and blood loss or transfusion rates in adult patients undergoing open lumbar spine surgery. METHODS: In this retrospective medical record review, the surgical records of 174 adult patients who underwent open, nonmicroscopically assisted lumbar spine surgery performed by a single surgeon at a single institution were evaluated. Maximum, minimum, and average temperature, hypothermic temperature, and temperature range parameters were compared with intraoperative, total, and net blood loss and blood transfusion parameters. Additional patient demographic and perioperative characteristics were compared with blood loss and transfusion parameters to determine potential confounders. Analysis of variance, Spearman rank correlation, and generalized multiple linear regression analysis were performed to test for an association between temperature and blood loss or allogeneic transfusion rates. Statistical significance was set at P≤.05. RESULTS: After implementation of exclusion criteria, 160 patient records and 168 surgical procedures were included in the analysis. For patients whose temperature decreased to a hypothermic level at some point during the procedure, hypothermic maximum temperature was protective against blood loss on bivariate analysis (P≤.02), but this finding lost significance after multivariate regression analysis (P>.09). Temperature range was associated with increased blood loss on bivariate analyses (P<.001) but also lost significance after adjusting for covariates in regression analysis (P≥.65). Surgery type (P≤.001) and operative time (P≤.001) were the most robust predictors of increased blood loss (P=.005) and were significantly associated with temperature (P<.001). CONCLUSION: No effect was found on perioperative blood loss from any temperature parameter or hypothermia in adult patients who underwent lumbar spine surgery once covariates were controlled for with multivariate analysis. One possible interpretation of these results is that the effect of temperature on blood loss can be explained by its strong relationship to the confounders of operative time and surgery type.