Use of an elastic-scattering spectroscopy and artificial intelligence device in the assessment of lesions suggestive of skin cancer: A comparative effectiveness study.

Background: Skin cancer is the most common form of cancer worldwide. As artificial intelligence (AI) expands its scope within dermatology, leveraging technology may aid skin cancer detection. Objective: To assess the safety and effectiveness of an elastic-scattering spectroscopy (ESS) device in evaluating lesions suggestive of skin cancer. Methods: This prospective, multicenter clinical validation study was conducted at 4 US investigational sites. Patients with skin lesions suggestive of melanoma and nonmelanoma skin cancers were clinically assessed by expert dermatologists and evaluated by a device using AI algorithms comparing current ESS lesion readings with training data sets. Statistical analyses included sensitivity, specificity, AUROC, negative predictive value (NPV), and positive predictive value (PPV). Results: Overall device sensitivity was 97.04%, with subgroup sensitivity of 96.67% for melanoma, 97.22% for basal cell carcinoma, and 97.01% for squamous cell carcinoma. No statistically significant difference was found between the device and dermatologist performance (P = .8203). Overall specificity of the device was 26.22%. Overall NPV of the device was 89.58% and PPV was 57.54%. Conclusion: The ESS device demonstrated high sensitivity in detecting skin cancer. Use of this device may assist primary care clinicians in assessing suspicious lesions, potentially reducing skin cancer morbidity and mortality through expedited and enhanced detection and intervention.

Artificial Intelligence-Based Assessment of Colorectal Polyp Histology by Elastic-Scattering Spectroscopy.

BACKGROUND: Colonoscopic screening and surveillance for colorectal cancer could be made safer and more efficient if endoscopists could predict histology without the need to biopsy and perform histopathology on every polyp. Elastic-scattering spectroscopy (ESS), using fiberoptic probes integrated into standard biopsy tools, can assess, both in vivo and in real time, the scattering and absorption properties of tissue related to its underlying pathology. AIMS: The objective of this study was to evaluate prospectively the potential of ESS to predict polyp pathology accurately. METHODS: We obtained ESS measurements from patients undergoing screening/surveillance colonoscopy using an ESS fiberoptic probe integrated into biopsy forceps. The integrated forceps were used for tissue acquisition, following current standards of care, and optical measurement. All measurements were correlated to the index pathology. A machine learning model was then applied to measurements from 367 polyps in 169 patients to prospectively evaluate its predictive performance. RESULTS: The model achieved sensitivity of 0.92, specificity of 0.87, negative predictive value (NPV) of 0.87, and high-confidence rate (HCR) of 0.84 for distinguishing 220 neoplastic polyps from 147 non-neoplastic polyps of all sizes. Among 138 neoplastic and 131 non-neoplastic polyps ≤ 5 mm, the model achieved sensitivity of 0.91, specificity of 0.88, NPV of 0.89, and HCR of 0.83. CONCLUSIONS: Results show that ESS is a viable endoscopic platform for real-time polyp histology, particularly for polyps ≤ 5 mm. ESS is a simple, low-cost, clinically friendly, optical biopsy modality that, when interfaced with minimally obtrusive endoscopic tools, offers an attractive platform for in situ polyp assessment.

Toward optical spectroscopy-guided lung biopsy: Demonstration of tissue-type classification.

The diagnostic yield of standard tissue-sampling modalities of suspected lung cancers, whether by bronchoscopy or interventional radiology, can be nonoptimal, varying with the size and location of lesions. What is needed is an insitu sensor, integrated in the biopsy tool, to objectively distinguish among tissue types in real time, not to replace biopsy with an optical diagnostic, but to verify that the sampling tool is properly located within the target lesion. We investigated the feasibility of elastic scattering spectroscopy (ESS), coupled with machine learning, to distinguish lung lesions from the various nearby tissue types, in a study with freshly-excised lung tissues from surgical resections. Optical spectra were recorded with an ESS fiberoptic probe in different areas of the resected pulmonary tissues, including benign-margin tissue sites as well as the periphery and core of the lesion. An artificial-intelligence model was used to analyze, retrospectively, 2032 measurements from excised tissues of 35 patients. With high accuracy, ESS was able to distinguish alveolar tissue from bronchi, alveolar tissue from lesions, and bronchi from lesions. This ex vivo study indicates promise for ESS fiberoptic probes to be integrated with surgical intervention tools, to improve reliability of pulmonary lesion targeting.

Optical scattering as an early marker of apoptosis during chemotherapy and antiangiogenic therapy in murine models of prostate and breast cancer.

Monitoring of the in vivo tumor state to track therapeutic response in real time may help to evaluate new drug candidates, maximize treatment efficacy, and reduce the burden of overtreatment. Current preclinical tumor imaging methods have largely focused on anatomic imaging (e.g., MRI, ultrasound), functional imaging (e.g., FDG-PET), and molecular imaging with exogenous contrast agents (e.g., fluorescence optical tomography). Here we utalize spatial frequency domain imaging (SFDI), a noninvasive, label-free optical technique, for the wide-field quantification of changes in tissue optical scattering in preclinical tumor models during treatment with chemotherapy and antiangiogenic agents. Optical scattering is particularly sensitive to tissue micro-architectural changes, including those that occur during apoptosis, an early indicator of response to cytotoxicity induced by chemotherapy, thermotherapy, cryotherapy, or radiation therapy. We utilized SFDI to monitor responses of PC3/2G7 prostate tumors and E0771 mammary tumors to treatment with cyclophosphamide or the antiangiogenic agent DC101 for up to 49 days. The SFDI-derived scattering amplitude was highly correlated with cleaved caspase-3, a marker of apoptosis (ρp = 0.75), while the exponent of the scattering wavelength-dependence correlated with the cell proliferation marker PCNA (ρp = 0.69). These optical parameters outperformed tumor volume and several functional parameters (e.g., oxygen saturation and hemoglobin concentration) as an early predictive biomarker of treatment response. Quantitative diffuse optical scattering is thus a promising new early marker of treatment response, which does not require radiation or exogenous contrast agents.

Optical Spectroscopy as a Method for Skin Cancer Risk Assessment.

Skin cancer is the most prevalent cancer, and its assessment remains a challenge for physicians. This study reports the application of an optical sensing method, elastic scattering spectroscopy (ESS), coupled with a classifier that was developed with machine learning, to assist in the discrimination of skin lesions that are concerning for malignancy. The method requires no special skin preparation, is non-invasive, easy to administer with minimal training, and allows rapid lesion classification. This novel approach was tested for all common forms of skin cancer. ESS spectra from a total of 1307 lesions were analyzed in a multi-center, non-randomized clinical trial. The classification algorithm was developed on a 950-lesion training dataset, and its diagnostic performance was evaluated against a 357-lesion testing dataset that was independent of the training dataset. The observed sensitivity was 100% (14/14) for melanoma and 94% (105/112) for non-melanoma skin cancer. The overall observed specificity was 36% (84/231). ESS has potential, as an adjunctive assessment tool, to assist physicians to differentiate between common benign and malignant skin lesions.

Elastic scattering spectroscopy for early detection of breast cancer: partially supervised Bayesian image classification of scanned sentinel lymph nodes.

Sentinel lymph node biopsy is a standard diagnosis procedure to determine whether breast cancer has spread to the lymph glands in the armpit (the axillary nodes). The metastatic status of the sentinel node (the first node in the axillary chain that drains the affected breast) is the determining factor in surgery between conservative lumpectomy and more radical mastectomy including axillary node excision. The traditional assessment of the node requires sample preparation and pathologist interpretation. An automated elastic scattering spectroscopy (ESS) scanning device was constructed to take measurements from the entire cut surface of the excised sentinel node and to produce ESS images for cancer diagnosis. Here, we report on a partially supervised image classification scheme employing a Bayesian multivariate, finite mixture model with a Markov random field (MRF) spatial prior. A reduced dimensional space was applied to represent the scanning data of the node by a statistical image, in which normal, metastatic, and nonnodal-tissue pixels are identified. Our results show that our model enables rapid imaging of lymph nodes. It can be used to recognize nonnodal areas automatically at the same time as diagnosing sentinel node metastases with sensitivity and specificity of 85% and 94%, respectively. ESS images can help surgeons by providing a reliable and rapid intraoperative determination of sentinel nodal metastases in breast cancer.

The color of cancer: Margin guidance for oral cancer resection using elastic scattering spectroscopy.

OBJECTIVES/HYPOTHESIS: To evaluate the usefulness of elastic scattering spectroscopy (ESS) as a diagnostic adjunct to frozen section analysis in patients with diagnosed squamous cell carcinoma of the oral cavity. STUDY DESIGN: Prospective analytic study. METHODS: Subjects for this single institution, institutional review board-approved study were recruited from among patients undergoing surgical resection for squamous cell cancer of the oral cavity. A portable ESS device with a contact fiberoptic probe was used to obtain spectral signals. Four to 10 spectral readings were obtained on each subject from various sites including gross tumor and normal-appearing mucosa in the surgical margin. Each reading was correlated with the histopathologic findings of biopsies taken from the exact location of the spectral readings. A diagnostic algorithm based on multidimensional pattern recognition/machine learning was developed. Sensitivity and specificity, error rate, and area under the curve were used as performance metrics for tests involving classification between disease and nondisease classes. RESULTS: Thirty-four (34) subjects were enrolled in the study. One hundred seventy-six spectral data point/biopsy specimen pairs were available for analysis. ESS distinguished normal from abnormal tissue, with a sensitivity ranging from 84% to 100% and specificity ranging from 71% to 89%, depending on how the cutoff between normal and abnormal tissue was defined (i.e., mild, moderate, or severe dysplasia). There were statistically significant differences in malignancy scores between histologically normal tissue and invasive cancer and between noninflamed tissue and inflamed tissue. CONCLUSIONS: This is the first study to evaluate the effectiveness of ESS in guiding mucosal resection margins in oral cavity cancer. ESS provides fast, real-time assessment of tissue without the need for pathology expertise. ESS appears to be effective in distinguishing between normal mucosa and invasive cancer and between "normal" tissue (histologically normal and mild dysplasia) and "abnormal" tissue (severe dysplasia and carcinoma in situ) that might require further margin resection. Further studies, however, are needed with a larger sample size to validate these findings and to determine the effectiveness of ESS in distinguishing visibly and histologically normal tissue from visibly normal but histologically abnormal tissue. LEVEL OF EVIDENCE: NA Laryngoscope, 127:S1-S9, 2017.

Flow arrest intra-arterial delivery of small TAT-decorated and neutral micelles to gliomas.

The cell-penetrating trans-activator of transcription (TAT) is a cationic peptide derived from human immunodeficiency virus-1. It has been used to facilitate macromolecule delivery to various cell types. This cationic peptide is capable of crossing the blood-brain barrier and therefore might be useful for enhancing the delivery of drugs that target brain tumors. Here we test the efficiency with which relatively small (20 nm) micelles can be delivered by an intra-arterial route specifically to gliomas. Utilizing the well-established method of flow-arrest intra-arterial injection we compared the degree of brain tumor deposition of cationic TAT-decorated micelles versus neutral micelles. Our in vivo and post-mortem analyses confirm glioma-specific deposition of both TAT-decorated and neutral micelles. Increased tumor deposition conferred by the positive charge on the TAT-decorated micelles was modest. Computational modeling suggested a decreased relevance of particle charge at the small sizes tested but not for larger particles. We conclude that continued optimization of micelles may represent a viable strategy for targeting brain tumors after intra-arterial injection. Particle size and charge are important to consider during the directed development of nanoparticles for intra-arterial delivery to brain tumors.

Safety, feasibility, and optimization of intra-arterial mitoxantrone delivery to gliomas.

Mitoxantrone is a highly cytotoxic antineoplastic drug, however, its poor penetration of the blood-brain barrier has limited its role in the treatment of brain cancers. We hypothesize that intra-arterial (IA) delivery of mitoxantrone may enhance its capacity for regional brain deposition thus expanding its potential as a brain tumor therapy agent. In this study we assessed the dose-response characteristics as well as the feasibility and safety of mitoxantrone delivery to the brain and specifically to gliomas in a rodent model. We show that delivery optimization utilizing the technique of intra-arterial transient cerebral hypoperfusion (IA-TCH) facilitates achieving the highest peak- and end- brain drug concentrations as compared to intravenous and IA delivery without hypoperfusion. Additionally, we observed significant tumor-specific uptake of mitoxantrone when delivered by the IA-TCH method. No untoward effects of IA-TCH delivery of mitoxantrone were observed. The IA-TCH method is shown to be a safely tolerated and feasible strategy for delivering mitoxantrone to tumors in the glioma model tested. Additional investigation is warranted to determine if IA-TCH delivery of mitoxantrone produces clinically relevant benefit.

Liposome size and charge optimization for intraarterial delivery to gliomas.

Nanoparticles such as liposomes may be used as drug delivery vehicles for brain tumor therapy. Particle geometry and electrostatic properties have been hypothesized to be important determinants of effective tumor targeting after intraarterial injection. In this study, we investigate the combined roles of liposome size and surface charge on the effectiveness of delivery to gliomas after intraarterial injection. Intracarotid injection of liposomes was performed in separate cohorts of both healthy and C6 glioma-bearing Sprague Dawley rats after induction of transient cerebral hypoperfusion. Large (200 nm) and small (60-80 nm) fluorescent dye-loaded liposomes that were either cationic or neutral in surface charge were utilized. Delivery effectiveness was quantitatively measured both with real-time, in vivo and postmortem diffuse reflectance spectroscopy. Semi-quantitative multispectral fluorescence imaging was also utilized to assess the pattern and extent of liposome targeting within tumors. Large cationic liposomes demonstrated the most effective hemispheric and glioma targeting of all the liposomes tested. Selective large cationic liposome retention at the site of glioma growth was observed. The liposome deposition pattern within tumors after intraarterial injection was variable with both core penetration and peripheral deposition observed in specific tumors. This study provides evidence that liposome size and charge are important determinants of effective brain and glioma targeting after intraarterial injection. Our results support the future development of 200-nm cationic liposomal formulations of candidate intraarterial anti-glioma agents for further pre-clinical testing.

Cationizable lipid micelles as vehicles for intraarterial glioma treatment.

The relative abundance of anionic lipids on the surface of endothelia and on glioma cells suggests a workable strategy for selective drug delivery by utilizing cationic nanoparticles. Furthermore, the extracellular pH of gliomas is relatively acidic suggesting that tumor selectivity could be further enhanced if nanoparticles can be designed to cationize in such an environment. With these motivating hypotheses the objective of this study was to determine whether nanoparticulate (20 nm) micelles could be designed to improve their deposition within gliomas in an animal model. To test this, we performed intra-arterial injection of micelles labeled with an optically quantifiable dye. We observed significantly greater deposition (end-tissue concentration) of cationizable micelles as compared to non-ionizable micelles in the ipsilateral hemisphere of normal brains. More importantly, we noted enhanced deposition of cationizable as compared to non-ionizable micelles in glioma tissue as judged by semiquantitative fluorescence analysis. Micelles were generally able to penetrate to the core of the gliomas tested. Thus we conclude that cationizable micelles may be constructed as vehicles for facilitating glioma-selective delivery of compounds after intraarterial injection.

Endoscopic histological assessment of colonic polyps by using elastic scattering spectroscopy.

BACKGROUND: Elastic-scattering spectroscopy (ESS) can assess in vivo and in real-time the scattering and absorption properties of tissue related to underlying pathologies. OBJECTIVES: To evaluate the potential of ESS for differentiating neoplastic from non-neoplastic polyps during colonoscopy. DESIGN: Pilot study, retrospective data analysis. SETTING: Academic practice. PATIENTS: A total of 83 patients undergoing screening/surveillance colonoscopy. INTERVENTIONS: ESS spectra of 218 polyps (133 non-neoplastic, 85 neoplastic) were acquired during colonoscopy. Spectral data were correlated with the classification of biopsy samples by 3 GI pathologists. High-dimensional methods were used to design diagnostic algorithms. MAIN OUTCOME MEASUREMENTS: Diagnostic performance of ESS. RESULTS: Analysis of spectra from polyps of all sizes (N = 218) resulted in a sensitivity of 91.5%, specificity of 92.2%, and accuracy of 91.9% with a high-confidence rate of 90.4%. Restricting analysis to polyps smaller than 1 cm (n = 179) resulted in a sensitivity of 87.0%, specificity of 92.1%, and accuracy of 90.6% with a high-confidence rate of 89.3%. Analysis of polyps 5 mm or smaller (n = 157) resulted in a sensitivity of 86.8%, specificity of 91.2%, and accuracy of 90.1% with a high-confidence rate of 89.8%. LIMITATIONS: Sample size, retrospective validation used to obtain performance estimates. CONCLUSION: Results indicate that ESS permits accurate, real-time classification of polyps as neoplastic or non-neoplastic. ESS is a simple, low cost, clinically robust method with minimal impact on procedure flow, especially when integrated into standard endoscopic biopsy tools. Performance on polyps 5 mm or smaller indicates that ESS may, in theory, achieve Preservation and Incorporation of Valuable Endoscopic Innovations performance thresholds. ESS may one day prove to be a useful tool used in endoscopic screening and surveillance of colorectal cancer.

Cerebral hypoperfusion-assisted intra-arterial deposition of liposomes in normal and glioma-bearing rats.

BACKGROUND: Optimizing liposomal vehicles for targeted delivery to the brain has important implications for the treatment of brain tumors. The promise of efficient, brain-specific delivery of chemotherapeutic compounds via liposomal vehicles has yet to be achieved in clinical practice. Intra-arterial injection of specially designed liposomes may facilitate efficient delivery to the brain and to gliomas. OBJECTIVE: To test the hypothesis that cationic liposomes may be effectively delivered to both normal and glioma-bearing brain tissue utilizing a strategy of intra-arterial injection during transient cerebral hypoperfusion. METHODS: Cationic, anionic, and neutral liposomes were separately injected via the internal carotid artery of healthy rats during transient cerebral hypoperfusion. Rats bearing C6 gliomas were similarly injected with cationic liposomes. Liposomes were loaded with DilC18(5) dye whose concentrations can be measured by light absorbance and fluorescence methods. RESULTS: After intra-arterial injection, a robust uptake of cationic in comparison with anionic and neutral liposomes into brain parenchyma was observed by diffuse reflectance spectroscopy. Postmortem multispectral fluorescence imaging revealed that liposomal cationic charge was associated with more efficient delivery to the brain. Cationic liposomes were also readily observed within glioma tissue after intra-arterial injection. However, over time, cationic liposomes were retained longer and at higher concentrations in the surrounding, peritumoral brain than in the tumor core. CONCLUSION: This study demonstrates the feasibility of cationic liposome delivery to brain and glioma tissue after intra-arterial injection. Highly cationic liposomes directly delivered to the brain via an intracarotid route may represent an effective method for delivering antiglioma agents.

Spatial mapping of drug delivery to brain tissue using hyperspectral spatial frequency-domain imaging.

We present an application of spatial frequency-domain imaging (SFDI) to the wide-field imaging of drug delivery to brain tissue. Measurements were compared with values obtained by a previously validated variation of diffuse reflectance spectroscopy, the method of optical pharmacokinetics (OP). We demonstrate a crosscorrelation between the two methods for absorption extraction and drug concentration determination in both experimental tissue phantoms and freshly extracted rodent brain tissue. These methods were first used to assess intra-arterial (IA) delivery of cationic liposomes to brain tissue in Sprague Dawley rats under transient cerebral hypoperfusion. Results were found to be in agreement with previously published experimental data and pharmacokinetic models of IA drug delivery. We then applied the same scheme to evaluate IA mitoxantrone delivery to glioma-bearing rats. Good correlation was seen between OP and SFDI determined concentrations taken from normal and tumor averaged sites. This study shows the feasibility of mapping drug/tracer distributions and encourages the use of SFDI for spatial imaging of tissues for drug/tracer-tagged carrier deposition and pharmacokinetic studies.

Cationic surface charge enhances early regional deposition of liposomes after intracarotid injection.

Rapid first pass uptake of drugs is necessary to increase tissue deposition after intraarterial (IA) injection. Here we tested whether brain tissue deposition of a nanoparticulate liposomal carrier could be enhanced by coordinated manipulation of liposome surface charge and physiological parameters, such as IA injection during transient cerebral hypoperfusion (TCH). Different degrees of blood-brain barrier disruption were induced by focused ultrasound in three sets of Sprague-Dawley rats. Brain tissue retention was then compared for anionic, cationic, and charge-neutral liposomes after IA injection combined with TCH. The liposomes contained a non-exchangeable carbocyanine membrane optical label that could be quantified using diffuse reflectance spectroscopy (DRS) or visualized by multispectral imaging. Real-time concentration-time curves in brain were obtained after each liposomal injection. Having observed greater tissue retention of cationic liposomes compared to other liposomes in all three groups, we tested uptake of cationic liposomes in C6 tumor bearing rats. DRS and multispectral imaging of postmortem sections revealed increased liposomal uptake by the C6 brain tumor as compared to non-tumor contralateral hemisphere. We conclude that regional deposition of liposomes can be enhanced without BBB disruption using IA injection of cationic liposomal formulations in healthy and C6 tumor bearing rats.

Elastic scattering spectroscopy as an optical marker of inflammatory bowel disease activity and subtypes.

BACKGROUND: In 10% to 15% of individuals, inflammatory bowel disease (IBD) is difficult to classify as ulcerative colitis (UC) or Crohn's disease (CD). Previous work has demonstrated that probe-based elastic scattering spectroscopy (ESS) can produce spectra, informed by parameters like tissue ultrastructure and hemoglobin content, capable of differentiating pathologies. This study investigates whether ESS is an in vivo optical biomarker for the presence, activity, and type of IBD in the colon. METHODS: Pilot study, a retrospective data analysis. ESS spectra of endoscopically normal and inflamed colon were obtained from 48 patients with IBD and 46 non-IBD controls. Measurements from patients with IBD were categorized as CD or UC based on clinical diagnosis. Spectra were analyzed using high-dimensional methods. Leave-one-patient-out cross-validation was used to obtain diagnostic performance estimates. RESULTS: Patients with IBD were distinguishable from non-IBD controls with a sensitivity of 0.93 and specificity of 0.91 based on readings from endoscopically normal mucosa, and 0.94 and 0.93 from inflamed mucosa. In patients with IBD, histologically normal and inflamed colon were distinguishable with per-class accuracies of 0.83 and 0.89, respectively; histologically normal from inactive inflammation with accuracies of 0.73 and 0.89, respectively; and inactive from active colitis with accuracies of 0.87 and 0.84, respectively. The diagnosis of CD versus UC was made with per-class accuracies of 0.92 and 0.87 in normal and 0.87 and 0.85 in inflamed mucosa, respectively. CONCLUSIONS: ESS, a simple, low-cost clinically friendly optical biopsy modality, has the potential to enhance the endoscopic assessment of IBD and its activity in real time and may help to distinguish CD from UC.

Transient cerebral hypoperfusion assisted intraarterial cationic liposome delivery to brain tissue.

Transient cerebral hypoperfusion (TCH) has empirically been used to assist intraarterial (IA) drug delivery to brain tumors. Transient (<3 min) reduction of cerebral blood flow (CBF) occurs during many neuro- and cardiovascular interventions and has recently been used to better target IA drugs to brain tumors. In the present experiments, we assessed whether the effectiveness of IA delivery of cationic liposomes could be improved by TCH. Cationic liposomes composed of 1:1 DOTAP:PC (dioleoyl-trimethylammonium-propane:phosphatidylcholine) were administered to three groups of Sprague-Dawley rats. In the first group, we tested the effect of blood flow reduction on IA delivery of cationic liposomes. In the second group, we compared TCH-assisted IA liposomal delivery versus intravenous (IV) administration of the same dose. In the third group, we assessed retention of cationic liposomes in brain 4 h after TCH assisted delivery. The liposomes contained a near infrared dye, DilC18(7), whose concentration could be measured in vivo by diffuse reflectance spectroscopy. IA injections of cationic liposomes during TCH increased their delivery approximately fourfold compared to injections during normal blood flow. Optical pharmacokinetic measurements revealed that relative to IV injections, IA injection of cationic liposomes during TCH produced tissue concentrations that were 100-fold greater. The cationic liposomes were retained in the brain tissue 4 h after a single IA injection. There was no gross impairment of neurological functions in surviving animals. Transient reduction in CBF significantly increased IA delivery of cationic liposomes in the brain. High concentrations of liposomes could be delivered to brain tissue after IA injections with concurrent TCH while none could be detected after IV injection. IA-TCH injections were well tolerated and cationic liposomes were retained for at least 4 h after IA administration. These results should encourage development of cationic liposomal formulations of chemotherapeutic drugs and their IA delivery during TCH.

Real-time hemodynamic response and mitochondrial function changes with intracarotid mannitol injection.

UNLABELLED: Disruption of blood brain barrier (BBB) is used to enhance chemotherapeutic drug delivery. The purpose of this study was to understand the time course of hemodynamic and metabolic response to intraarterial (IA) mannitol infusions in order to optimize the delivery of drugs for treating brain tumors. PRINCIPAL RESULTS: We compared hemodynamic response, EEG changes, and mitochondrial function as judged by relative changes in tissue NADH concentrations, after intracarotid (IC) infusion of equal volumes of normal saline and mannitol in our rabbit IC drug delivery model. We observed significantly greater, though transient, hyperemic response to IC infusion of mannitol compared to normal saline. Infusion of mannitol also resulted in a greater increase in tissue NADH concentrations relative to the baseline. These hemodynamic, and metabolic changes returned to baseline within 5min of mannitol injection. CONCLUSION: Significant, though transient, changes in blood flow and brain metabolism occur with IA mannitol infusion. The observed transient hyperemia would suggest that intravenous (IV) chemotherapy should be administered either just before, or concurrent with IA mannitol injections. On the other hand, IA chemotherapy should be delayed until the peak hyperemic response has subsided.

Real-time pathology to guide breast surgery: seeing alone is not believing.

Tissue diagnostic techniques based on optical spectroscopy, in various incarnations, are approaching clinical reality for intraoperative guidance of surgical procedures. Examination of tissue properties by elastic light-scattering spectroscopy may constitute a preferable alternative to frozen-section pathology or touch imprint cytology for intraoperative assessment of resection margins during breast-conserving surgery.

Advances in optics for biotechnology, medicine and surgery.

The editors introduce the Biomedical Optics Express feature issue, "Advances in Optics for Biotechnology, Medicine and Surgery," which includes 12 contributions from attendees of the 2011 conference Advances in Optics for Biotechnology, Medicine and Surgery XII.