Longitudinal optical monitoring of blood flow in breast tumors during neoadjuvant chemotherapy.

We measure tissue blood flow markers in breast tumors during neoadjuvant chemotherapy and investigate their correlation to pathologic complete response in a pilot longitudinal patient study (n = 4). Tumor blood flow is quantified optically by diffuse correlation spectroscopy (DCS), and tissue optical properties, blood oxygen saturation, and total hemoglobin concentration are derived from concurrent diffuse optical spectroscopic imaging (DOSI). The study represents the first longitudinal DCS measurement of neoadjuvant chemotherapy in humans over the entire course of treatment; it therefore offers a first correlation between DCS flow indices and pathologic complete response. The use of absolute optical properties measured by DOSI facilitates significant improvement of DCS blood flow calculation, which typically assumes optical properties based on literature values. Additionally, the combination of the DCS blood flow index and the tissue oxygen saturation from DOSI permits investigation of tissue oxygen metabolism. Pilot results from four patients suggest that lower blood flow in the lesion-bearing breast is correlated with pathologic complete response. Both absolute lesion blood flow and lesion flow relative to the contralateral breast exhibit potential for characterization of pathological response. This initial demonstration of the combined optical approach for chemotherapy monitoring provides incentive for more comprehensive studies in the future and can help power those investigations.

Diffuse Optics for Tissue Monitoring and Tomography.

This review describes the diffusion model for light transport in tissues and the medical applications of diffuse light. Diffuse optics is particularly useful for measurement of tissue hemodynamics, wherein quantitative assessment of oxy- and deoxy-hemoglobin concentrations and blood flow are desired. The theoretical basis for near-infrared or diffuse optical spectroscopy (NIRS or DOS, respectively) is developed, and the basic elements of diffuse optical tomography (DOT) are outlined. We also discuss diffuse correlation spectroscopy (DCS), a technique whereby temporal correlation functions of diffusing light are transported through tissue and are used to measure blood flow. Essential instrumentation is described, and representative brain and breast functional imaging and monitoring results illustrate the workings of these new tissue diagnostics.

Comparison of adenosine echocardiography, with and without isometric handgrip, to exercise echocardiography in the detection of ischemia in patients with coronary artery disease.

This study was undertaken to evaluate whether adenosine echocardiography is comparable to exercise echocardiography in the detection of ischemia in patients with suspected coronary artery disease and to assess whether the addition of handgrip exercise to adenosine enhances the induction of ischemia in these patients. Accordingly, 67 patients with suspected or known coronary artery disease referred for exercise testing underwent adenosine, adenosine with handgrip, and post-treadmill exercise echocardiography. A maximal adenosine infusion dose of 170 micrograms/kg/min was used. Images at baseline and during each of the three stress modalities were digitized in a quad-screen format, randomized, and blinded as to the stage and mode of intervention for nonbiased interpretation. An ischemic response was defined as a new or worsening wall motion abnormality. Ischemia was detected by exercise echocardiography (n = 20) more often than by adenosine echocardiography alone (n = 11; p = 0.039) but similarly to adenosine plus handgrip (n = 16; difference not significant). Exact agreement in individual response between exercise adenosine echocardiography was seen in 51 (80%) of 64 patients and increased to 88% between exercise and adenosine plus handgrip. In the patients who underwent angiography (n = 45), the sensitivity for coronary artery disease (n = 33) was 87% for adenosine, 91% for adenosine plus handgrip, and 93% for exercise echocardiography. The respective sensitivities decreased to 64%, 81%, and 89% in patients without previous myocardial infarction. Specificity was 91% for adenosine with or without handgrip and 82% for exercise echocardiography. Image quality during adenosine with and without handgrip was superior to that during exercise (p < 0.01). Thus in patients with coronary artery disease able to exercise, exercise echocardiography induces ischemia more frequently than does adenosine echocardiography alone. The addition of handgrip exercise to adenosine infusion enhances the detection of ischemia without reducing specificity or image quality and is recommended when adenosine echocardiography is used as a pharmacologic stress test.

Clinical impact of transesophageal echocardiography in the diagnosis and management of infective endocarditis.

Transesophageal echocardiography (TEE) has assumed a prominent role in the diagnosis and management of infective endocarditis (IE). The impact of negative TEE findings on the management of patients suspected of having IE is not clear. To better understand how a negative TEE examination would influence patient management, the medical records of 93 consecutive patients undergoing TEE to evaluate for IE were examined. The influence of TEE was assessed based on changes in diagnosis, antibiotic therapy, or the need for surgical intervention during hospitalization. The negative predictive value of TEE was found to be 100% in native valves and 90% in prosthetic valves. The overall impact of negative TEE findings was significant in terms of final diagnosis and duration of antibiotic therapy (a negative TEE resulted in 60% reduction in antibiotic duration, p = 0.0001). These findings suggest that in patients with native heart valves, a negative TEE examination virtually excludes IE. In patients with prosthetic valves, a negative TEE significantly decreases the likelihood of IE but does not completely exclude the diagnosis; therefore, in this setting, a negative finding should be closely correlated with the clinical course.

Left ventricular pseudoaneurysm complicating mitral valve replacement: transesophageal echocardiographic diagnosis and impact on management.

Left ventricular pseudoaneurysm formation after mitral valve replacement, although infrequent, is a serious complication with potential catastrophic results. We describe a case of an anterobasal pseudoaneurysm compressing all branches of the left coronary artery, which was missed by initial transthoracic echocardiography and was well characterized with the transesophageal approach. Although the pseudoaneurysm was detected at contrast ventriculography, the transesophageal study provided new specific details regarding the exact site of origin of the pseudoaneurysm and its relationship to the coronary arteries that significantly influenced planning the surgical procedure and patient management.

Hydrolytic enzymes of Euglena gracilis: characterization and activity as a function of culture age and carbon deprivation.

Optimal assay conditions are described for 8 hydrolases of Euglena gracilis var. bacillaris, SM-L1 (streptomycin-bleached) strain, 7 of which have an acid pH-optimum. Acid-phosphatase, beta-galactosidase, beta-glucosidase, b-fucosidase, cathepsin D, RNase, DNase, and an esterase are active in cell homogenates. Amylase has very low activity, and beta-glucuronidase, arylsulfatase, beta, N-acetyl-glucosaminidase, alpha-fucosidase, and alpha- and beta-mannosidase are inactive.