Search

INTRODUCTION DSC-MRI perfusion methods are commonly used to evaluate both primary and metastatic brain cancer with the creation of maps of relative cerebral blood volume (rCBV). Recently, guidelines were established to ensure a standard DSC-MRI acquisition protocol that reduces inter-site variability. The purpose of this study was to initiate the determination of rCBV benchmark values using the DSC-MRI consensus protocol in treatment-naïve brain metastases. METHODS Patients from three sites with treatment-naïve, contrast-enhancing brain metastases on MRI were considered for inclusion in this retrospective study. The MRIs included pre- and post-contrast T1w(T1+C) images obtained after administration of gadolinium-based contrast agent (GBCA) (0.1 mmol/kg), which serves as the recommended preload for the DSC-MRI data collection. A 2nd GBCA dose (0.1 mmol/kg) was administered 40-60sec after the collection of baseline GRE-EPI images using recommended settings (FA=60o, TE/TR=30ms/1100-1250ms) for 120s. Calibrated pre/post T1w difference maps (dT1) were used for delineation of enhancing lesion, and standardized (calibrated) rCBV (sRCBV) created. Mean sRCBV for metastases were compared to normal appearing white matter (NAWM) and treatment-naive glioblastoma (GBM) from a previous study. Pairwise comparisons were performed using the Mann-Whitney nonparametric test. RESULTS N=52 patients with primary histology of lung (n=27); breast (n=6); skin (n=7); gastrointestinal (GI: n=3) and genitourinary (GU: n=9) cancers were included in comparison to GBM (n=31). The mean sRCBV for all metastases (1.77+/-1.05) is significantly lower (p=0.0003) than for GBM (2.67+/-1.34) but with both statistically greater (p< 0.0001) than NAWM (0.706+/-0.163). Individually, lung (1.47+/- 0.61), breast (2.275+/-0.87), skin (2.10+/-1.22), GI (1.91+/- 0.64) and GU (2.01+/-0.63) mean sRCBV are statistically greater than for NAWM. CONCLUSION Using the consensus DSC-MRI acquisition protocol confirms use of sRCBV to identify biologically active, treatment-naive brain metastases setting benchmark values for future applications.

There are currently no approved drugs to treat Zika virus (ZIKV) infection during pregnancy. Hyperimmune globulin products such as VARIZIG and WinRho are FDA-approved to treat conditions during pregnancy such as Varicella Zoster virus infection and Rh-incompatibility. We administered ZIKV-specific human immune globulin as a treatment in pregnant rhesus macaques one day after subcutaneous ZIKV infection. All animals controlled ZIKV viremia following the treatment and generated robust levels of anti-Zika virus antibodies in their blood. No adverse fetal or infant outcomes were identified in the treated animals, yet the placebo control treated animals also did not have signs related to congenital Zika syndrome (CZS). Human immune globulin may be a viable prophylaxis and treatment option for ZIKV infection during pregnancy, however, more studies are required to fully assess the impact of this treatment to prevent CZS.

Congenital Zika virus (ZIKV) exposure results in a spectrum of disease ranging from severe birth defects to delayed onset neurodevelopmental deficits. ZIKV-related neuropathogenesis, predictors of birth defects, and neurodevelopmental deficits are not well defined in people. Here we assess the methodological and statistical feasibility of a congenital ZIKV exposure macaque model for identifying infant neurobehavior and brain abnormalities that may underlie neurodevelopmental deficits. We inoculated five pregnant macaques with ZIKV and mock-inoculated one macaque in the first trimester. Following birth, growth, ocular structure/function, brain structure, hearing, histopathology, and neurobehavior were quantitatively assessed during the first week of life. We identified the typical pregnancy outcomes of congenital ZIKV infection, with fetal demise and placental abnormalities. We estimated sample sizes needed to define differences between groups and demonstrated that future studies quantifying brain region volumes, retinal structure, hearing, and visual pathway function require a sample size of 14 animals per group (14 ZIKV, 14 control) to detect statistically significant differences in at least half of the infant exam parameters. Establishing the parameters for future studies of neurodevelopmental outcomes following congenital ZIKV exposure in macaques is essential for robust and rigorous experimental design.

Ultrasound elasticity imaging has demonstrated utility in breast imaging, but it is typically performed with handheld transducers and two-dimensional imaging. Two-dimensional (2D) elastography images tissue stiffness of only a plane and hence suffers from errors due to out-of-plane motion, whereas three-dimensional (3D) data acquisition and motion tracking can be used to track out-of-plane motion that is lost in 2D elastography systems. A commercially-available automated breast volume scanning system that acquires 3D ultrasound data with precisely controlled elevational movement of the 1D array ultrasound transducer was employed in this study. A hybrid, guided 3D motion tracking algorithm was developed that first estimated the displacements in one plane using a modified quality-guided search method, and then performed an elevational guided-search for displacement estimation in adjacent planes. To assess the performance of the method, 3D radiofrequency echo data were acquired with this system from a phantom and from an in vivo human breast. For both experiments, the axial displacement fields were smooth and high cross-correlation coefficients were obtained in most of the tracking region. The motion tracking performance of the new method was compared with a correlation-based exhaustive search method on six consecutive volumes (five consecutive volume pairs) of radiofrequency echo data acquired during in vivo scanning of the breast of one subject. For all five motion tracking volume pairs, the average motion-compensated cross-correlation values (between pre-deformation and motion-compensated post-deformation echo fields) obtained by the guided-search motion tracking method were equivalent to those by the exhaustive search method, and the computation time was about a factor of 10 less. Therefore, the proposed 3D ultrasound elasticity imaging method was a more efficient approach to produce a high quality of 3D ultrasound strain image.

Pulse oximetry is an important diagnostic tool in monitoring and treating both in-patients and ambulatory patients. Modern pulse oximeters exploit different body sites (eg fingertip, forehead or earlobe). All those are bulky and uncomfortable, resulting in low patient compliance. Therefore, we evaluated the accuracy and precision of a wrist-sensor pulse oximeter (Oxitone-1000, Oxitone Medical) vs. the traditional fingertip device. Fifteen healthy volunteers and 23 patients were recruited. The patient group included chronic obstructive pulmonary disease (COPD) (N = 8), asthma (N = 6), sarcoidosis (N = 5) and others. Basic demographic data, skin tone type, smoking status and medical history were recorded. Blood oxygen level (SpO2) and pulse-rate values were determined by a non-invasive pulse oximeter (Reference, a conventional FDA-cleared fingertip pulse oximeter) and by Oxitone-1000. All tests were performed in singleton and in a blinded fashion. The measurements were done in sitting and standing positions, as well as after a 6-min walk test. The mean age was 60.4 ± 9.83 years, 55% were male. No significant differences were observed between the wrist-sensor and the traditional fingertip pulse oximeters in all tested parameters. Mean SpO2 was 96.45% vs. 97.18% and the mean pulse was 74.64 vs. 74.6 bpm (Oxitone-1000 vs. Reference, respectively, p

Background In utero Zika virus (ZIKV) infection causes birth defects and neurodevelopmental deficits in neonates. We reasoned that a translational macaque model of congenital ZIKV infection could define disease pathophysiology not possible in human clinical studies. Methods We inoculated 5 pregnant rhesus macaques with a Puerto Rican isolate of ZIKV (ZIKV-PRVABC59) during the first trimester, monitored infection with plasma viral RNA (vRNA) loads, and evaluated infants for birth defects and neurodevelopmental deficits during their first week of life. Assessments included neurobehavioral assessments, ophthalmic examinations, optical coherence tomography, electroretinography with visual evoked potentials, hearing examinations, brain magnetic resonance imaging (MRI), and tissue histopathological analyses. Results All five pregnant dams demonstrated plasma viremia and seroconversion following ZIKV inoculation. One of the five pregnancies resulted in a stillbirth. All liveborn infants had decreased feeding volumes and weight gain compared with control infants. A comprehensive voxel-based morphometric comparison of ZIKV-exposed and control infant brain MRIs identified increased gray matter volume and density in the frontal lobe in the ZIKV-exposed infant group, which corresponds to the pharyngeal motor cortex responsible for coordinating swallowing. Ocular studies identified differences between ZIKV-exposed and control infants in retinal layer thicknesses (inner plexiform, outer nuclear layers, photoreceptor outer segment) and visual evoked potentials (increased amplitude of waveforms). While ZIKV vRNA was detected in the decidua of 2/5 pregnancies, no ZIKV vRNA was identified in infant tissues and none of the infants developed an anti-ZIKV IgM response. Conclusion In utero ZIKV exposure resulted in decreased feeding volumes and weight gain, which may be related to the gray matter changes identified in the pharyngeal motor cortex. Changes in retinal layer thicknesses and increased cortical visual pathway waveform amplitude suggest vision may be impaired. These changes occurred despite the lack of evidence of vertical transmission, suggesting that ZIKV exposure without measurable vertical transmission affects fetal brain development. Disclosures All authors: No reported disclosures.

Congenital Zika virus (ZIKV) infection impacts fetal development and pregnancy outcomes. We infected a pregnant rhesus macaque with a Puerto Rican ZIKV isolate in the first trimester. The pregnancy was complicated by preterm premature rupture of membranes (PPROM), intraamniotic bacterial infection and fetal demise 49 days post infection (gestational day 95). Significant pathology at the maternal-fetal interface included acute chorioamnionitis, placental infarcts, and leukocytoclastic vasculitis of the myometrial radial arteries. ZIKV RNA was disseminated throughout fetal tissues and maternal immune system tissues at necropsy, as assessed by quantitative RT-PCR for viral RNA. Replicating ZIKV was identified in fetal tissues, maternal uterus, and maternal spleen by fluorescent in situ hybridization for viral replication intermediates. Fetal ocular pathology included a choroidal coloboma, suspected anterior segment dysgenesis, and a dysplastic retina. This is the first report of ocular pathology and prolonged viral replication in both maternal and fetal tissues following congenital ZIKV infection in a rhesus macaque. PPROM followed by fetal demise and severe pathology of the visual system have not been described in macaque congenital ZIKV infection previously. While this case of ZIKV infection during pregnancy was complicated by bacterial infection with PPROM, the role of ZIKV on this outcome cannot be precisely defined, and further nonhuman primate studies will determine if increased risk for PPROM or other adverse pregnancy outcomes are associated with congenital ZIKV infection.

Congenital Zika virus (ZIKV) infection impacts fetal development and pregnancy outcomes. We infected a pregnant rhesus macaque with a Puerto Rican ZIKV isolate in the first trimester. The pregnancy was complicated by preterm premature rupture of membranes (PPROM) and fetal demise 49 days post infection (gestational day 95). Significant pathology at the maternal-fetal interface included acute chorioamnionitis, placental infarcts, and leukocytoclastic vasculitis of the myometrial radial arteries. ZIKV RNA was disseminated throughout the fetus tissues and maternal immune system at necropsy, as assessed by quantitative RT-PCR for viral RNA. Replicating ZIKV was identified in fetal tissues, maternal lymph node, and maternal spleen by fluorescent in situ hybridization for viral replication intermediates. Fetal ocular pathology included a choroidal coloboma, suspected anterior segment dysgenesis, and a dysplastic retina. This is the first report of ocular pathology and prolonged viral replication in both maternal and fetal tissues following congenital ZIKV infection in rhesus macaques. PPROM followed by fetal demise and severe pathology of the visual system have not been described in macaque congenital infection previously; further nonhuman primate studies are needed to determine if an increased risk for PPROM is associated with congenital Zika virus infection.Author summaryA ZIKV infection during pregnancy is associated with malformations in fetal development including, but not limited to, ocular and brain anomalies, such as microcephaly, and stillbirth. The development of an accurate pregnancy model to study the effects of ZIKV will provide insight into vertical transmission, ZIKV tissue distribution, and fetal injury and malformations. Non-human primates closely resemble human in terms of the reproductive system, immunity, placentation and pregnancy. Our study demonstrates that the rhesus macaque is a compelling model in which to study ZIKV during pregnancy due to similar outcomes between the human and rhesus macaque. These similarities include prolonged viremia, vertical transmission, adverse pregnancy outcomes and fetal pathology, including defects in the visual system.

Infection with Zika virus (ZIKV) is associated with human congenital fetal anomalies. To model fetal outcomes in nonhuman primates, we administered Asian-lineage ZIKV subcutaneously to four pregnant rhesus macaques. While non-pregnant animals in a previous study contemporary with the current report clear viremia within 10-12 days, maternal viremia was prolonged in 3 of 4 pregnancies. Fetal head growth velocity in the last month of gestation determined by ultrasound assessment of head circumference was decreased in comparison with biparietal diameter and femur length within each fetus, both within normal range. ZIKV RNA was detected in tissues from all four fetuses at term cesarean section. In all pregnancies, neutrophilic infiltration was present at the maternal-fetal interface (decidua, placenta, fetal membranes), in various fetal tissues, and in fetal retina, choroid, and optic nerve (first trimester infection only). Consistent vertical transmission in this primate model may provide a platform to assess risk factors and test therapeutic interventions for interruption of fetal infection. The results may also suggest that maternal-fetal ZIKV transmission in human pregnancy may be more frequent than currently appreciated.Author summaryMaternal ZIKV infection in pregnancy is associated with severe fetal anomalies, including microcephaly. It has been shown that infection manifests differently in pregnancy than in the non-pregnant state, with prolonged maternal viremia. ZIKV is spread by mosquitos and through sexual contact and since its first detection in early 2015, has become endemic to the Americas. While much has been learned from studying infected human pregnancies, there are still many questions concerning transmission of ZIKV from mother to fetus. Investigating ZIKV infection in non-human primates could help answer these questions due to similarities in the immune system, and the tissues separating the fetus from the mother during pregnancy. Our study serves to model ZIKV transmission in early and late pregnancy, as well as study the effects of this infection on the fetus and mother at these different times in pregnancy. The data collected provides an important insight on ZIKV in pregnancy where the pregnancies have been monitored throughout the entire infection period until term, and suggests that vertical transmission may be very efficient, although severe fetal outcomes are uncommon.

Diagnostic tools for evaluating the supraorbital rim in preparation for nerve decompression surgery in patients with chronic headaches are currently limited. We evaluated the use of sonography to diagnose the presence of a supraorbital notch or foramen in 11 cadaver orbits. Sonographic findings were assessed by dissecting cadaver orbits to determine whether a notch or foramen was present. Sonography correctly diagnosed the presence of a supraorbital notch in 7 of 7 cases and correctly diagnosed a supraorbital foramen in 4 of 4 cases. We found that sonography had 100% sensitivity in diagnosing a supraorbital notch and foramen. This tool may therefore be helpful in characterizing the supraorbital rim preoperatively and may influence the decision to use a transpalpebral or endoscopic approach for supraorbital nerve decompression as well as the decision to use local or general anesthesia.

A possibly causal relationship between multiple sclerosis and chronic cerebrospinal venous insufficiency has recently been hypothesized. Studies investigating chronic cerebrospinal venous insufficiency have reported conflicting results and few have employed multiple diagnostic imaging modalities across a large patient and control population. In this study, three complementary imaging modalities were used to investigate the chronic cerebrospinal venous insufficiency hypothesis in patients with multiple sclerosis and two age- and sex-matched control groups: healthy volunteers and patients with other neurological diseases. Strictly blinded Doppler ultrasound according to the original chronic cerebrospinal venous insufficiency hypothesis; four-dimensional flow magnetic resonance imaging of venous flow in the head, neck, and chest; and contrast-enhanced magnetic resonance venography for neck and chest venous luminography were acquired. An internal jugular vein stenosis evaluation was also performed across modalities. Percentage of subjects meeting ultrasound-based chronic cerebrospinal venous insufficiency criteria was small and similar between groups. In group-wise and pairwise testing, no four-dimensional flow magnetic resonance imaging variables were statistically significantly different, for any measurement location. In contrast-enhanced magnetic resonance venography of the internal jugular and azygos veins, no statistically significant differences were observed in stenosis scores between groups. These results represent compelling evidence against the chronic cerebrospinal venous insufficiency hypothesis in multiple sclerosis.

Three-dimensional sonography is being cited more frequently as a means of further evaluating the patient and better defining the pathological condition. One of the main limitations of fully implementing 3D imaging in the sonography department is the limited experience and limited time to educate working sonographers on how to fully understand and use this technology. Deliberate and planned educational activities designed to meet the educational needs of working sonographers may be a way to increase the clinical use of 3D technology in the clinical sonography department.

The stiffness of the uterine cervix changes during pregnancy, significantly softening at term. A pathologically rapid softening can result in preterm birth. Shear Wave Elasticity Imaging (SWEI) methods can be used to track these changes. Difficulties of in vivo human research during pregnancy motivate the study of animal models with anatomy and physiology similar to humans. This work presents preliminary results of the use of SWEI methods to assess cervical stiffness changes during pregnancy in a rhesus macaque non-human primate (NHP) model. Pregnant NHP subjects are being scanned during two consecutive menstrual cycles before pregnancy and five times between weeks 4 to 23 after conception and once two weeks after delivery. Shear waves are remotely induced with an Acoustic Radiation Force Impulse excitation within regions of interest (ROIs) centered in the uterine end of cervix. Shear wave speed (SWS) was quantified with different estimators and at various ROI locations to choose the more consistent and precise estimates. From 25 subjects currently enrolled, 8 have successfully completed the study. At late pregnancy, SWS values significantly decreased to less than 40% of their pre-pregnancy values, and recovered two weeks after delivery. SWS changes in the same subject at early pregnancy compared to pre-pregnancy and late-pregnancy values were statistically significant. Our results motivate further investigation of SWEI to track cervical softening during pregnancy in the NHP model.

The drugs cisplatin and gentamicin are given consecutively to various cancer patients suffering from infections. Little information exists about the ultrastructural alterations of kidney glomeruli caused by treatment with these drugs. Renal glomeruli of guinea pigs treated with cisplatin alone and in combination with gentamicin were studied by transmission electron microscopy. The findings revealed foci of damage induced by cisplatin and especially by cisplatin/gentamicin in all glomerular components: glomerular capillaries, including their endothelial cells; basement membrane, epithelial podocytes, mesangial cells, and parietal cells of Bowman's capsule. The damage was expressed by endothelial cytoplasmic extrusions into the vascular lumen, thickening and lamination of capillary basement membrane, focal foot process fusion of podocytes, vacuolization in cytoplasm of endothelial cells of epithelial podocytes and of parietal cells, and the presence of lipid bodies and myeloid bodies in all glomerular cell types. Additionally, injurious effects to cytoplasmic organelles such as mitochondria, nuclei, and endoplasmic reticulum were observed. The results indicate that cisplatin alone and in combination with gentamicin is toxic to renal glomerular tissue. Since these drugs were previously found toxic for strial capillaries in the inner ear and since the main glomerular component is the glomerular capillaries, potential vascular damage and vascular complications in different body systems have to be taken into consideration when these drugs are needed in clinical use.

An interlaboratory study of shear wave speed (SWS) estimation was performed. Commercial shear wave elastography systems from Fibroscan, Philips, Siemens and Supersonic Imagine, as well as several custom laboratory systems, were involved. Fifteen sites were included in the study. CIRS manufactured and donated 11 pairs of custom phantoms designed for the purposes of this investigation. Dynamic mechanical tests of equivalent phantom materials were also performed. The results of this study demonstrate that there is very good agreement among SWS estimation systems, but there are several sources of bias and variance that can be addressed to improve consistency of measurement results.

The vesiculo-vacuolar organelle (VVO) is a recently described organelle found in the cytoplasm of endothelial cells that line tumor microvessels and normal venules. VVOs are grape-like clusters of interconnecting uncoated vesicles and vacuoles, bounded by trilaminar unit membranes, that span the entire thickness of vascular endothelium, thereby providing a potential transendothelial connection between the vascular lumen and the extravascular space. Macromolecular tracers preferentially cross hyperpermeable tumor microvessels through VVOs. The present investigation was undertaken to elucidate further the ultrastructure and function of VVOs in a murine ovarian carcinoma (MOT) and in normal venules. Morphometry revealed that VVOs were enormous cytoplasmic structures (median area, 0.12–0.14 μm2 in single electron micrographs). Moreover, the individual vesicles and vacuoles that comprised VVOs were on average substantially larger than capillary caveolae and followed a non-normal distribution that was skewed to the right. Specimen tilting provided conclusive evidence that individual VVO vesicles and vacuoles communicated with each other and with the endothelial cells’ plasma membranes by stomata, some of which were closed by diaphragms composed of a single membrane. Studies with two tracers, ferritin (FE, diameter ~ 11 nm) and horseradish peroxidase (HRP, diameter ~ 5 nm), revealed that passage of macromolecules through VVOs was regulated at the level of stomatal diaphragms, thereby demonstrating a mechanism for controlling the passage of macromolecules across endothelial cells. Thus, compared with tumor microvessels, little circulating FE and HRP entered the VVOs of normal venular endothelium because stomata joining vesicles and vacuoles to each other and to the lumen and ablumen were closed. VVOs and their component vesicles/vacuoles were readily distinguished from endosomal organelles such as coated vesicles and multivesicular bodies, which also accumulated FE and HRP. Our findings indicate that VVOs provide a major pathway for the extravasation of circulating macromolecules across endothelia taller than capillary endothelium and suggest that upregulated VVO function accounts for the well-known hyperpermeability of tumor blood vessels.

The damaging effects on the liver tissue of treatment with cisplatin followed by the aminoglycoside antibiotic gentamicin were studied in guinea pigs. The ultrastructural findings revealed foci of damage in the liver parenchyma, including its vascular component. Injurious effects to cytoplasmatic organelles such as mitochondria and endoplasmic reticulum as well as to nuclei were observed. In addition, abundance of lysosomes, autophagic vacuoles, and amorphous-granular bile in the lumina of bile canaliculi was found. Focal sinusoidal lining damage and capillarization of sinusoids were also present. In vascular lumina, some erythrocytes showed a deformed shape ("ropalocytosis"). Taken together, these findings indicate that the combined treatment with cisplatin followed by gentamicin is toxic to components of liver tissue. Since toxic changes have been shown in vessels of the inner ear and in renal-glomerular capillaries, the present observations of hepatotoxicity indicate the potential vascular damage to various tissues. The injurious effects of the cisplatin-aminoglycoside combination should be considered during its use in clinical conditions.

A previous study demonstrated that, in generalized granuloma annulare in the epidermis, the Langerhans' cell section area and the number of Langerhans' cell granules or Birbeck granules per cell section were increased, suggesting an active state of these Langerhans' cells. Reexamination by transmission electron microscopy of the same tissue, but in samples also containing dermal tissue, from the same subjects revealed endothelial cells with rod-shaped bodies resembling Birbeck granules or Birbeck granule-like structures. This finding has not been previously described in blood vessels of human skin and is described here.

In the present study, Langerhans' cells (LCs) in the sacral epidermis, 8-10 cm from lesions of patients (mean age 71 years) with decubital ulcers, were compared ultrastructurally and morphometrically with those in the patients' own normal epidermis from the upper leg, before and after supplementation with 50 mg/day elementary zinc (in the form of a 220-mg tablet of Avazinc, administered once daily) for four months. Zinc intake resulted in from 80% to full healing of the decubital ulcers in the patients studied. The percentages of LCs were low in both perilesional sacral epidermis (2.07 +/- 0.71%) and in control leg epidermis (2.71 +/- 1.38%) before zinc supplementation and also afterward (2.12 +/- 0.16% and 2.59 +/- 0.88%, respectively). LCs demonstrated a more dendritic morphology after zinc supplementation: 68.15 +/- 9.28% and 77.0 +/- 3.45% of sacral and of control leg epidermal LCs, respectively, had dendrites before, and 91.52 +/- 3.43% and 84.15 +/- 3.64% of sacral and of control leg epidermal LCs, respectively, had dendrites after zinc supplementation. The LC section area in the sacral epidermis near the lesion as well as in the control leg epidermis and the number of LC granules in LC sections were not affected by zinc supplementation. The higher percentage of LCs having dendrites in the epidermis of patients with decubital ulcers after zinc supplementation may indicate that these LCs are in a more motile state, which might affect the healing process of the lesions.

Purpose: The generalized spectrum (GS) has been used to quantify nonrandomness of scattering sources and to characterize breast and liver tissues. In this work, we implement a multitaper GS approach creating parametric images of GS features that describe the degree of nonrandom structure in breast lesions. Methods: This IRB‐approved, HIPAA compliant study recruited subjects who were scheduled for core biopsy of a suspicious breast mass. Subjects were scanned with a Siemens Acuson S2000 using a linear array transducer at 15MHz. Radiofrequency (RF) echo data were obtained in radial (parallel to breast lactiferous ducts) and antiradial planes. Cases (n=34) were selected based on the availability of biopsy results and a lesion size of at least 3mm in both planes. The multitaper GS was obtained by computing the correlation matrix of the Fourier transform of RF signal segments tapered by Prolate Spheroidal Sequences. Nonrandomness was quantified by parameterizing the collapsed average of the GS. A region of interest (ROI) within each lesion and each plane was defined,and the mean and standard deviation of the nonrandomness within it were computed. Results: Cases were grouped into: fibroadenoma (n=12, median diameter (MD)=7.6mm),other benign(n=11, MD=8.2mm), invasive ductal carcinoma (IDC) (n=5, MD=6.3mm), and other malignant(n=6, MD=6.9mm). The IDC nonrandomness inter‐case median of the mean and standard deviation was 64% and 59% of the values from other lesions, and the fractional difference in the standard deviation of the nonrandomness between the radial and antiradial views for the IDC cases was 59% smaller than the values for other lesions. Conclusion: Preliminary results indicate that the spatial distribution of scatterers within IDCs is more homogeneously random compared to other lesions. However, inter‐case variability was comparable to the median values. Future work will expand the population and use beam steered acquisitions to test for anisotropy in these features. This work was supported, in part, by NIH (grants R01CA111289, R21HD061896, R21HD063031, and R01HD072077) and the Consejo Nacional de Ciencia y Tecnologia of Mexico (Reg. 206414).

Purpose: Quantitative ultrasound (QUS) provides acoustic parameters that are closely related to tissue microstructure and sound wave propagation. This study evaluated a Bayesian classifier applied to breast QUS data to aid in differentiating benign from malignant masses. This presentation outlines methodology for deriving these quantitative parameters and reports preliminary results using the classifier on a small data set of human tumors. Methods: This IRB‐approved, HIPAA compliant study recruited 35 subjects who were scheduled for core biopsy of a suspicious breast mass. A Siemens S2000 scanner equipped with linear array transducers was used to acquire radiofrequency echo data at beam‐steered angles from −10 to 10 degrees from the normal to the transducer surface in both longitudinal and transverse planes. Echo signals also were obtained from a reference phantom using the same settings. Parameters included acoustic attenuation (ATT), backscatter coefficients (BSC), effective scatterer diameter (ESD), and a scatterer size heterogeneity index(HI). ATT and BSC within the tumor were estimated using a reference phantom method, while theESD was estimated from the BSC using a Gaussian form factor. HI was taken to be the standard deviation among the ESD estimates. A Bayesian classifier was designed to differentiate between Fibroadenoma and carcinoma. The data were divided into training (18 patients) and testing (17 patients) sets. Classification was performed using the minimum distance to the centroid of the training class and the results were compared with the biopsy results. Results: The best performance with a parameter pair (ATT, ESD) was about 80% which increased to about 100% with three parameters (ATT, ESD, HI). However, more verification studies are needed to include a larger data set and more specific tumor categories. Conclusion: QUS with a Bayesian classifier is a promising noninvasive tool to characterize breast tumors. This work was supported, in part, by NIH (grants R01CA111289, R21HD061896, R21HD063031, and R01HD072077) and the Consejo Nacional de Ciencia y Tecnologia of Mexico (Reg. 206414).

An ultrastructural and morphometric study compared Langerhans' cells in sacral epidermis, 8-10 cm from the lesion of patients (mean age 70) with decubital ulcers, with those in the patients' own normal epidermis from the upper leg and with those in the epidermis from the upper leg of normal age-matched volunteers. The Langerhans' cell section area was significantly lower in patients' control leg epidermis (25.86 +/- 2.29 microns2) than in that from normal controls (35.74 +/- 3.76 microns2) or that from patients' sacral epidermis near the lesion (41.26 +/- 3.45). The number of Langerhans' cell granules was higher in control leg epidermis of patients (10.22 +/- 1.26) and was significantly higher in lesioned sacral epidermis (12.94 +/- 1.90) than in normal controls (6.97 +/- 1.47). In Langerhans' cells in patients' epidermis, formative stages of Langerhans' cell granules were observed. The findings may indicate that Langerhans' cells in patients' epidermis are in an active state.

Langerhans' cells in the sacral epidermis 8-10 cm from the lesion of elderly patients (mean age 74 years) with decubital ulcers were studied ultrastructurally and compared with the patients' own normal epidermis from the upper leg, with age-matched normal controls, and with young normal controls (mean age 43 years). High percentages of Langerhans' cells (ranging between 30 and 50%) without dendrites were found in patient epidermis from the sacral region near the lesion and similar percentages in normal skin from the patients' upper leg. In both elderly and young controls, Langerhans' cells without dendrites found in the epidermis of the upper leg were fewer, ranging between 13 and 33%. The density of Langerhans' cells in adjacent sites of the same epidermis was non-homogeneous, being in the range of 0.56-1.19% in patient sacral epidermis, 0.69-1.31% in patient normal leg epidermis, 0.63-4.17% in leg epidermis of the elderly controls, and 0.63-3.94% in leg epidermis of the young controls. The majority of the Langerhans' cells in both patients and controls were located near the basal cell layer and in the mid-epidermis. The percentage of Langerhans' cells found in patient sacral epidermis (0.84 +/- 0.08%) and in their leg epidermis (0.87 +/- 0.15%) was significantly lower than in the elderly controls (1.91 +/- 0.30%) and young controls (1.84 +/- 0.24%). The low percentage of Langerhans' cells in the epidermis of patients with decubital ulcers may affect the healing process of the lesions.

The toxic effects on the stria vascularis of treatment with cisplatin alone and combined with the aminoglycoside antibiotic, gentamicin, were studied in guinea pigs. The toxicity induced in albino and pigmented guinea pigs was investigated morphologically with light and transmission electron microscopy, and functionally by brainstem-evoked response audiometry. The results of hearing thresholds were variable, ranging from no change in one ear in some of the animals to a hearing loss of 20 dB in one or both ears when treated with low-dose cisplatin alone or in combination with gentamicin. Bilateral deafness resulted from high-dose cisplatin combined with gentamicin. The combined treatment produced prominent structural damage in the stria vascularis. The results should be considered when aminoglycoside therapy is required in conjunction with cisplatin.

Etioplasts were isolated from leaves of 9-day-old etiolated maize (Zea mays L.) seedlings and incubated in a relatively simple medium in light and in the dark. During the first 5 h no changes occurred in the fine structure of the isolated etioplasts in the dark. In light the size of the prolamellar bodies decreased and significantly more plastid sections without prolamellar bodies were counted. The total length of the thylakoids per plastid section increased, but there was no evidence for bi- and polythylakoid formation. It is concluded that light induces the structural transformation of the prolamellar body membranes into primary thylakoids also in isolated etioplasts.

Langerhans' cells were studied in the epidermis of two patients with active Behçet's disease and compared with those in two normal controls. Ultrastructural morphology and the percentage of Langerhans' cells found were similar in patients' (1.88%) and the control epidermis (1.79%). The density of Langerhans' cells in adjacent sites of the same epidermis was not homogeneous, being in the range of 0.8-2.8% in Behçet's disease and 0.6-4% in the controls. In the controls, Langerhans' cells were distributed unevenly. Some were located near the basal layer of the epidermis while the rest were in the mid and upper layers. In Behçet's disease most Langerhans' cells were in the mid-epidermis, but some were immediately beneath the stratum granulosum. In the Behçet's disease epidermis the area occupied by Langerhans' cells was increased by about 25% and the number of granules found increased by about 44%. It is suggested that in Behçet's disease the Langerhans' cells are in a more active state.

Langerhans' cells were studied in the epidermis of two patients with Granuloma Annulare (GA) of the generalized type and compared with those in two normal controls. The percentage of Langerhans' cells in the GA epidermis population was 3.4% and in the control, 1.8%. The density of Langerhans' cells in different adjacent sites of the same epidermis was not uniform, being in the range of 0.9–5% in GA and 0.6–4% in controls. In the GA epidermis, the Langerhans' cell section area was increased by about 40% and the number of Langerhans' cell granules found per cell section by about 41%. The findings may indicate that, in granuloma annulare epidermis, the Langerhans' cells are in a more active state.

The structural dimensions of capillary tight junctions and the uptake of 99mTc pertechnetate in human gliomas were studied. Quantitative analysis revealed a correlation between the uptake of radionuclides and the length of endothelial tight junctions. It is suggested that brain scintigraphy might be used for the selection of malignant brain tumors with altered tight junctions which might be accessible to chemotherapy with water-soluble agents.

The toxic effects of cisplatin (cis-diamminedichloroplatinum [II]) on the organ of Corti are well established. Few and conflicting data on this drug's effects on the stria vascularis exist. The present study presents animal experiments on the toxic effects of cisplatin in the stria vascularis and in the organ of Corti. Cisplatin-induced toxicity in albino and pigmented guinea pigs was evaluated morphologically and functionally, using light and transmission electron microscopy as well as auditory brainstem-evoked potentials on the organ of Corti and the stria vascularis. The results showed variability in hearing thresholds, ranging from no change to hearing loss of 30 dB, and prominent damage in the organ of Corti and in the stria vascularis. The toxic effects to both the organ of Corti and the stria vascularis should be considered when cisplatin is used in chemotherapy.