Centimeters Of Tissue Research Articles

Model‐based optoacoustic inversions with incomplete projection data

Optoacoustic imaging is an emerging noninvasive imaging modality that can resolve optical contrast through several millimeters to centimeters of tissue with diffraction-limited resolution of ultrasound. Yet, quantified reconstruction of tissue absorption maps requires optoacoustic signals to be collected from as many locations around the object as possible. In many tomographic imaging scenarios, however, only limited-view or partial projection data are available, which has been shown to generate image artifacts and overall loss of quantification accuracy. In this article, the recently introduced interpolated-matrix-model optoacoustic inversion method is tested in different limited-view scenarios and compared to the standard backprojection algorithm. Both direct (TGSVD) and iterative (PLSQR) regularization methods are proposed to improve the accuracy of image reconstructions with their performance tested on simulated and experimental data. While for full-view tomographic data the model-based inversion has been generally shown to attain higher reconstruction accuracy compared to backprojection algorithms, the incomplete tomographic datasets lead to ill-conditioned forward matrices and, consequently, to error-prone inversions, with strong artifacts following a distinct ripple-type pattern. The proposed regularization techniques are shown to stabilize the inversion and eliminate the artifacts. Overall, it has been determined that the regularized interpolated-matrix-model-based optoacoustic inversions show higher accuracy than reconstructions with the standard backprojection algorithm. Finally, the combination of model-based inversion with PLSQR or TGSVD regularization methods can lead to an accurate reconstruction of limited-projection angle optoacoustic data and practical systems for optoacoustic imaging in many realistic cases where the full-view dataset is unavailable.

Gold nanorod light scattering labels for biomedical imaging

Gold nanorods can be used as extremely bright labels for differential light scattering measurements using two closely spaced wavelengths, thereby detecting human disease through several centimeters of tissue in vivo. They have excellent biocompatibility, are non-toxic, and are not susceptible to photobleaching. They have narrow, easily tunable plasmon spectral lines and thus can image multiple molecular targets simultaneously. Because of their small size, gold nanorods can be transported to various tissues inside the human body via the vasculature and microvasculature, and since they are smaller than vascular pore sizes, they can easily cross vascular space and enter individual cells.

Sensitivity of molecular target detection by multispectral optoacoustic tomography (MSOT)

Optoacoustic imaging is emerging as a noninvasive imaging modality that can resolve optical contrast through several millimeters to centimeters of tissue with the resolution achieved by ultrasound imaging. More recently, applied at multiple illumination wavelengths, multispectral optoacoustic tomography (MSOT) offered the ability to effectively visualize tissue biomarkers by resolving their distinct spectral signatures. While the imaging potential of the method has been demonstrated, little is known on the sensitivity performance in resolving chromophoric and fluorescent substances, such as optical functional and molecular reporters. Herein the authors investigate the detection capacity and physical limits of tomographic optoacoustic imaging by simulating signals originating from absorbing spheres in tissue-mimicking media. To achieve this, a modified optoacoustic equation is employed to incorporate wavelength-dependent propagation and attenuation of diffuse light and ultrasound. The theoretical predictions are further validated in phantom experiments involving Cy5.5, a common near-infrared fluorescent molecular agent.

Image-guided Raman spectroscopic recovery of canine cortical bone contrast in situ.

Raman scattering provides valuable biochemical and molecular markers for studying bone tissue composition with use in predicting fracture risk in osteoporosis. Raman tomography can image through a few centimeters of tissue but is limited by low spatial resolution. X-ray computed tomography (CT) imaging can provide high-resolution image-guidance of the Raman spectroscopic characterization, which enhances the quantitative recovery of the Raman signals, and this technique provides additional information to standard imaging methods. This hypothesis was tested in data measured from Teflon tissue phantoms and from a canine limb. Image-guided Raman spectroscopy (IG-RS) of the canine limb using CT images of the tissue to guide the recovery recovered a contrast of 145:1 between the cortical bone and background. Considerably less contrast was found without the CT image to guide recovery. This study presents the first known IG-RS results from tissue and indicates that intrinsically high contrasts (on the order of a hundred fold) are available.

Sensitivity and Depth Penetration of Continuous Wave Versus Frequency-domain Photon Migration Near-infrared Fluorescence Contrast-enhanced Imaging ¶

The development of near-infrared fluorescent contrast agents and imaging techniques depends on the deep penetration of excitation light through several centimeters of tissue and the sensitive collection of the re-emitted fluorescence. In this contribution, the sensitivity and depth penetration of various fluorescence-enhanced imaging studies is surveyed and compared with current studies using continuous wave (CW) and frequency-domain photon migration (FDPM) measurements with planar wave illumination of modulated excitation light at 100 MHz and area collection of reemitted fluorescent light using a previously developed modulated intensified charge-coupled device camera system. Fluorescence was generated from nanomolar to micromolar solutions of indocyanine green (ICG) in a 100 μL volume submerged at 1–4 cm depths in a 1% Liposyn® solution to mimic tissue scattering properties. Enhanced depth penetration and sensitivity are achieved with optimal filter rejection of excitation light, and FDPM rejection of background light is not achieved using CW methods. We show the ability to detect as few as 100 fmol of ICG from area illumination of 785 nm light (5.5 mW/cm2) and FDPM area collection of 830 nm fluorescent light generated from 3 cm below the phantom surface. The lowered noise floor of FDPM measurements enables greater sensitivity and penetration depth than comparable CW measurements.

Effect of Percutaneous Nephrolithotripsy on Renal Function: Assessment with Quantitative SPECT of 99mTc-DMSA Renal Scintigraphy

To measure the effect of PCNL on global and regional renal function using quantitative single-photon emission CT (SPECT) measurement of Tc-dimercaptosuccinic acid (DMSA) uptake by the kidneys (QDMSA). A series of 47 male and 41 female patients with a mean age of 47 +/- 16 years were studied by sequential QDMSA examinations before and 1.5 to 24 months after PCNL. Among the 67 patients (76%) in whom PCNL was performed using upper- or lower-pole access, the function of the affected and nonaffected poles of the treated kidney was calculated separately. There was no statistically significant difference in the uptake by the treated kidneys before versus after PCNL (11.9% +/- 5% v 11.6% +/- 5%; t = 0.9; P = 0.368). The total functional volume of the treated kidney was slightly decreased, from 235 cc +/- 62 cc to 224 cc +/- 59 cc (t = 2.7; P = 0.011). The percent of the injected isotope dose per cubic centimeter of tissue of the treated kidney was not affected (0.051 +/- 0.02 v 0.053 +/- 0.02; t = 0.86; P = 0.296). Regional assessment revealed a statistically significant decrease in the functional volume at the PCNL port of entry (91 cc +/- 30 cc v 82 cc +/- 27 cc; t = 2.64; P = 0.013). Regarding the percent of the injected dose per cubic centimeter of renal tissue, no statistically significant difference was found between the area of the kidney that underwent PCNL and the untreated area of the same kidney (0.049 +/- 0.02 v 0.05 +/- 0.02; t = 0.693; P = 0.494). The function of the contralateral kidneys remained unchanged (13.4% +/- 5.2% v 13.6% +/- 4.8%; t = 0.68; P = 0.5). Despite the statistically significant decrease in the functional volume of the surgically treated region, neither total percent uptake nor percent of injected dose were reduced significantly. Further studies with long-term follow-up of treated kidneys are required.

Seeing into cells. The promise of in vivo molecular imaging in oncology.

Medicine is undergoing a revolution. Disease is increasingly being redefined in terms of underlying molecular abnormalities, as opposed to the signs and symptoms of the patient. This new definition is referred to as the ‘molecular signature’ of a disease and the current developments in biomedical research are accordingly termed ‘molecular medicine’. In the case of cancer, we know that tumours result from genetic alterations of cells, which may involve overexpression or underexpression of normal genes, or mutations that generate abnormal gene products. This may affect any of the molecules within the cell, the cell membrane or the cancer‐cell milieu. In addition, the microenvironment of a tumour, including stromal and vascular endothelial cells, is important for the growth and persistence of the tumour. This entire constellation of the abnormal molecular biology of tumour cells and their microenvironment is the molecular signature of cancer (Hanahan & Weinberg, 2000). > The greatest potential value of molecular imaging is its ability to report on the molecular state of a tumour in its normal milieu One consequence of this new understanding of disease is the increased effort to develop targeted drugs that interact specifically with the altered genes or their products and either limit the progression of or kill tumour cells. The hope is that such therapeutics will selectively target tumour cells and leave normal cells untouched, thereby reducing the common side effects of current anticancer therapies such as radio‐ and chemotherapy. There is an increasing number of such targeted therapeutics being developed and made available for clinical use. For example, until about five years ago, there were few options available for treating colon cancer beyond surgically removing the affected part of the colon and using standard chemotherapy. However, since 1999, the US Food and Drug Administration (FDA) has approved at least five targeted drugs …

Sensitivity and depth penetration of continuous wave versus frequency-domain photon migration near-infrared fluorescence contrast-enhanced imaging.

The development of near-infrared fluorescent contrast agents and imaging techniques depends on the deep penetration of excitation light through several centimeters of tissue and the sensitive collection of the re-emitted fluorescence. In this contribution, the sensitivity and depth penetration of various fluorescence-enhanced imaging studies is surveyed and compared with current studies using continuous wave (CW) and frequency-domain photon migration (FDPM) measurements with planar wave illumination of modulated excitation light at 100 MHz and area collection of reemitted fluorescent light using a previously developed modulated intensified charge-coupled device camera system. Fluorescence was generated from nanomolar to micromolar solutions of indocyanine green (ICG) in a 100 microL volume submerged at 1-4 cm depths in a 1% Liposyn solution to mimic tissue scattering properties. Enhanced depth penetration and sensitivity are achieved with optimal filter rejection of excitation light, and FDPM rejection of background light is not achieved using CW methods. We show the ability to detect as few as 100 fmol of ICG from area illumination of 785 nm light (5.5 mW/cm2) and FDPM area collection of 830 nm fluorescent light generated from 3 cm below the phantom surface. The lowered noise floor of FDPM measurements enables greater sensitivity and penetration depth than comparable CW measurements.

Positron emission tomography scan in cortical visual loss in patients with organophosphate intoxication

ObjectiveTo determine the cerebral metabolism of patients with cortical visual loss. DesignTwo observational case studies. TestingTwo patients who survived acute organophosphate poisoning with respiratory failure experienced severe visual loss despite relatively normal ophthalmic examination results. Magnetic resonance imaging of the brain revealed no abnormality of the visual system in either patient. Positron emission tomography (PET) was performed in these 2 patients and in 12 normal subjects with fluorine-18 fluorodeoxyglucose (FDG) as a tracer to measure cerebral glucose metabolism for the estimation of neurologic deficit in the visual cortex. Main outcome measuresThe FDG uptake values were measured as nanoCurie per cubic centimeters of tissue (nCi/cc). The relative uptake index in visual cortex was computed as the ratio of uptake of FDG in each region of visual cortex to that of cerebellum (regional visual cortex/cerebellum). ResultsHypometabolism was observed in the visual cortex of both patients. The relative uptake index of FDG in visual cortex (visual cortex/cerebellum) was significantly decreased in those patients compared with normal subjects. ConclusionsIn patients with cortical visual loss, conventional neuroimaging techniques can fail to visualize damage that can be detected by PET scanning, and PET analysis may be helpful in estimating the metabolic deficit of visual cortex and in establishing the organic nature of cortical visual loss in these patients.

Improvement of X-ray beam quality for treating cancer using double focus electric field strings.

Accurate knowledge of the distribution and amount of contamination electrons arising from the gantry head at the surface and in the first few centimeters of tissue is essential for the clinical practice of radiation oncology. These electrons tend to increase the surface dose and deteriorate the buildup in the radiation field compared with a pure photon field. In this study, the relative quantity and reduction of contamination electrons in a therapeutic radiation photon beam (15 MV) was investigated. The contamination electrons can be separated out by a special device. This device, consisting of a double-focus electric field (8 x 10(5) V/m) made by a large number of strings 2 x 10(-4) m in diameter, removes contamination electrons and positrons without affecting the photon beam. It is located under the tray holder. In clinical practice, the device can decrease the relative surface charge and relative surface dose due to contamination electrons in the photon beam used in radiation therapy.

Serial sectioning of thick tissue with a novel vibrating blade microtome

Vibrating blade microtomes are used extensively in biological research to section non-frozen tissue. There are a wide variety of commercial instruments available for this purpose, however, they are designed to cut thin sections primarily from a tissue block less than one centimeter in height. Herein is described a simple modification of a microscope frame that creates a vibrating blade microtome capable of producing a sequential series of sections through three centimeters of tissue. We illustrate the use of this device to identify and reconstruct a column of rat spinal motor neurons retrogradely labeled from a peripheral muscle. Themes: Cellular and molecular biology Topics: Staining, tracing and imaging techniques

Percussion and physical diagnosis: Separating myth from science

There are three percussion sounds, which are easily distinguishable by objective measures: tympany (heard with percussion over the intestines), resonance (heard over the normal lung), and dullness (heard over the liver or thigh). The percussion sound that is produced reflects the ease with which the body wall vibrates, which in turn is influenced by many variables, including the strength of the stroke, the condition and state of the body wall, and the underlying organs. Underlying organs or disease may cause dullness to occur at distant sites. There is good interobserver agreement among clinicians with regard to calling a particular percussion sound dull, resonant, or hyperresonant. In contrast, there is very poor interobserver agreement among clinicians using percussion to measure the span of a particular organ. The use of comparative percussion can detect most large pleural effusions, but this method is able to detect only a few pneumonias. Shifting dullness is a reliable and fairly accurate sign for the detection of ascites. Both of these techniques can still be recommended after a review of the literature. Topographic percussion (e.g., using percussion to locate the heart, liver, and spleen borders or dimensions) has poor reproducibility, is significantly inaccurate in many patients, and has little clinical utility; it should be abandoned. Its fundamental principle—that sound waves penetrate only several centimeters of tissue, resulting in a note reflecting abnormalities only in this layer of tissue—is incorrect. Auscultatory percussion offers no advantage over conventional percussion, with the possible exception of auscultatory percussion of the shoulder. Auscultatory percussion should be abandoned as a bedside diagnostic technique.

Morphological factors influencing transepithelial conductance in a rabbit model of ileitis

Background & Aims: Infection of rabbits with coccidia ( Eimeria magna) causes chronic ileal inflammation and diarrhea. Inflamed ileum also shows decreased transmural conductance. The aim of this study was to characterize morphological factors known to affect paracellular permeability that may alter transmural conductance in inflamed ileum. Methods: Ileal mucosa was mounted in Ussing chambers for study of [ 3H]mannitol and [ 3H]inulin fluxes. Light and electron microscopy were used for morphometric studies. Alterations in the zonula occludens of epithelial cells were evaluated in freeze-fracture replicas. Results: Inflamed ileum showed diminished paracellular fluxes. Inoculated rabbits showed marked lymphoplasmocytic infiltration and villus blunting in ileum. Villus linear junctional density was unaffected. However, total villus apical surface area per square centimeter of tissue was reduced in inflamed ileum, causing a diminished total villus linear junctional pathway per square centimeter of apical surface. Villus zonula occludens strand number was reduced in inflamed ileum, whereas the frequency of both villus and crypt lateral surface extrajunctional strands increased. Conclusions: Chronic inflammation exerts a profound effect on ileal paracellular permeability. Morphological data suggest that this effect may be caused in part by alterations in inflamed ileal mucosal structure and tight junctional organization and density, particularly on villi.

Modeling to Optimize Operational Practices to Limit Shallow Dose and Dose to the Lens at the Weldon Spring Site Remedial Action Project

The Weldon Spring Site Remedial Action Project (WSSRAP) began remediation of its chemical plant buildings in June 1992. The chemical plant was used by the Atomic Energy Commission in the 1950's and 1960's to process uranium ore and natural thorium. Many remaining equipment surfaces were highly contaminated with uranium and thorium product residues, which are relatively weak gamma emitters, but are strong beta emitters that deposit the majority of their energy within the first centimeter of tissue. An essential part of the remediation, therefore, is to control the dose to the skin, extremities, and the lens of the eye from the broad range of betas emitted by uranium and thorium decay series radionuclides. The WSSRAP planned to quantitatively record the dose to the skin, extremities, and the lens of the eye, when warranted, through selection and use of appropriate passive dosimeters. That would not, however, constitute control. A direct-reading instrument was needed that could be used by field technicians to anticipate and prevent work methods and situations that would otherwise result in the unnecessary commitment of dose. However, the interpretation of real-time instrument readings produced by a broad spectrum of beta energies is typically challenging at best, particularly when the shallow dose rate and the lens dose rate are both of interest. The purpose of this effort was, therefore, to (1) select a direct-reading instrument for use in the buildings that could be used to provide rule-of-thumb action levels for field technicians, which, if exceeded, would warrant worker protective measures; (2) determine the approximate conversions between the instrument readings and the shallow (including extremity) dose rate and lens of the eye dose rate; and (3) specify protective measures and dosimetry for the lens of the eye, if warranted. Methods described in the literature are used to estimate action levels for direct instrument readings and to demonstrate that lens dosimetry and special protective measures for the lens of the eye are not necessary at the WSSRAP.

Wavelength dependence of the differential pathlength factor and the log slope in time-resolved tissue spectroscopy.

The monitoring of tissue oxygenation by the technique of near infrared spectroscopy (NIRS) was first described by Jobsis in 1977 (Jobsis, 1977). The technique relies upon the relative transparency of tissue to near infrared (NIR) light to enable measurements of changes in optical attenuation across many centimetres of tissue. Early NIRS measurements could only derive qualitative changes in tissue and blood oxygenation from the observed variations in tissue attenuation (Brazy et al., 1985). However, data on the optical pathlength of light in tissue, measured by time resolved techniques employing picosecond laser pulses, have now permitted a quantitative analysis of attenuation measurements to be made (Delpy et al., 1988; Wyatt et al., 1990a). By incorporating information on the optical pathlength into a modified Beer-Lambert law it is possible to quantify changes in chromophore concentration from the measured changes in tissue attenuation. The optical pathlength needed in this calculation, the Differential Pathlength (DP) is defined as the local gradient in a plot of the attenuation measured in a scattering medium versus the absorption coefficient of the medium (Cope et al., 1991a; Cope, 1991b). It has been shown in previous studies (Delpy et al., 1988) that the DP can be approximated by measuring the mean distance that a picosecond light pulse travels across the tissue. Furthermore, a dimensionless multiplying factor, the Differential Pathlength Factor (DPF), can be obtained when the DP is divided by the geometric distance between light source and detector on the tissue surface. This factor has been shown, both theoretically and experimentally, to be approximately constant for any tissue once the optode spacing is larger than about 25 mm (van der Zee et al., 1990; van der Zee et al, in press), enabling clinical NIRS measurements to be made with varying optode geometries.

Modeling sickle cell vasoocclusion in the rat leg: quantification of trapped sickle cells and correlation with 31P metabolic and 1H magnetic resonance imaging changes.

We have developed an animal model to elucidate the acute effects of perfusion abnormalities on muscle metabolism induced by different density-defined classes of erythrocytes isolated from sickle cell anemia patients. Technetium-99m (99mTc)-labeled, saline-washed normal (AA), homozygous sickle (SS), or high-density SS (SS4) erythrocytes were injected into the femoral artery of the rat and quantitative 99mTc imaging, 31P magnetic resonance spectroscopy by surface coil at 2 teslas, and 1H magnetic resonance imaging at 0.15 tesla were performed. Between 5 and 25 microliters of SS4 cells was trapped in the microcirculation of the thigh (or 1-6 x 10(7) cells per cubic centimeter of tissue). In contrast, fewer SS discocytes (SS2) or AA cells were trapped (an equivalent packed cell volume of less than 6.7 microliters and 0.3 microliters, respectively). After injection of SS4 cells an initial increase in inorganic phosphate was observed in the region of the thigh served by the femoral artery, intracellular pH decreased, and subsequently the proton relaxation time T1 reached a broad maximum at 18-28 hr. When T1 obtained at this time was plotted against the volume of cells trapped, an increase of T1 over the control value of 411 +/- 48 msec was found that was proportional to the number of cells trapped. We conclude that the densest SS cells are most effective at producing vasoocclusion. The extent of the change detected by 1H magnetic resonance imaging is dependent on the amount of cells trapped in the microcirculation and the magnitude of the initial increase of inorganic phosphate.

Arterial platelet accumulation in experimental hypercholesterolemia

Accumulation of arterial platelets was calculated from 51Cr radioactivity in the intima-inner media of flushed, perfuse-fixed aortas and branch vessels of cynomolgus monkeys 48 hours after labeling of the blood platelets. In normocholesterolemic controls the radioactivity per square centimeter of tissue was consistently higher in aortic branching sites (circumostial aorta) than in the remainder of the aorta. In monkeys given 10 and 100 days of hypercholesterolemic diet radioactivity rose in circumostial aorta in proportion to increases in the remainder of the aorta. Focally high counts were found in gross fatty streaks and in areas of Evans blue uptake. In branch artery inner wall, where intimal changes were minimal and usually absent, counts were significantly greater in animals given 100 days of hypercholesterolemic diet than in controls. After 10 days of hypercholesterolemic diet the mean radioactivity in aortic branch artery inner wall uniformly exceeded control values, but usually nonsignificantly, permitting the speculation that changes in platelet-intima interactions may occur in widespread fashion throughout the arterial tree very early in hypercholesterolemia when lesion formation is incipient or absent.

Radiation exposure measurements in the 8-15 kVp X-ray range.

Exposure measurements are described for a typical Grenz-ray-ray machine operating in the 8–15 kVp energy range. The previously acknowledged energy dependence and sensitivity limitation of available instrumentation compromised the precision of such exposure measurements. Thus, users of Grenz-ray-ray machines, X-ray diffraction instruments, and other low-energy X-ray devices were often deluded into assuming the absence of ionizing radiations, as determined by use of conventional survey meters which were calibrated for higher energies. Although the first centimeter of tissue almost completely absorbs X-ray photons of this energy, their effects to such superficial sites, as the lens of the eye, are of concern. Commercially available detectors, of known energy dependence and sensitivity were used to measure primary and secondary levels of exposure to occupancy points. 10 mR/hr exposure rates were measured as far as 6 ft away from a scattering phantom irradiated by a 15 kVp primary beam.

Comparison of Biological Effects of Whole-Body Irradiation with 22.5-Mev X-Rays, 18-Mev Electrons, and 400-Kev X-Rays in the Rat

Recently, two types of high-energy irradiations, 22.5-Mev peak X-rays and 18Mev electrons, have been available for biological use from the University of Illinois medical betatron. The availability of these high-energy radiations for therapeutic purposes has raised important questions as to whether there are any qualitative or quantitative differences between the biological effects of the high-energy radiations and the conventional lower-energy radiations. Quastler et al. (1-4) found that the highand low-energy X-rays acted on mice qualitatively in the same way. He also noted that there were quantitative differences in the effects of highand low-energy radiations on mice. Haas et al. (5) have shown that the efficiency (,) of 22.5-Mev peak X-radiation compared with 200-kev peak X-radiation was approximately 0.56 for erythema of rabbit skin and 0.67 for epilation of rabbit skin. The large differences in depth dose characteristics of the 22.5-Mev peak X-ray beam and the 18-Mev electron beam have been described (6, 7). With the 22.5Mev peak X-ray beam, the dose increases with increasing depth in the first few centimeters of tissue, the maximum depth dose occurring at about 4.5 cm. With the 18-Mev electron beam, no marked increase in dose occurs near the surface. The experiments reported here were planned to compare the effects of the highenergy betatron irradiations with those of lower-energy irradiations from a conventional 400-kev peak therapy machine under experimental conditions where the differences in depth dose distribution were eliminated. The main objective of these experiments was to ascertain whether any qualitative differences exist between the

Carcinoma of the breast.

The Approach to the diagnosis of cancer of the breast usually has omitted the x-ray examination (1, 2). This may have been justified on the basis of the inconclusive results previously reported by numerous investigators in this field, (7, 19, 20, 24, 25, 27, 29). Now, however, with improved x-ray technics (13, 14), adequately checked against pathological findings (15, 23), a reconsideration of the x-ray examination as a routine procedure in the diagnosis of early mammary carcinoma is warranted. Technic A lateral and a tangential view of each breast, either in the erect or recumbent position, probably are adequate for survey purposes (4, 6, 11), but an additional “spot film” with a small cone in either the lateral or tangential direction is required for the examination of the diseased breast (16). The application of a small lead shot to the skin over the lesion, with scotch tape, helps the radiologist select the proper area for particular scrutiny. Non-screen films are used. Type A industrial fine-grain films are slightly superior but require more critical control of exposure factors. The breast is lightly compressed between the cone and the film. A fine-focus tube is used and the film-target distance varies. The optimum factors for an adult fatty breast are: 30 to 32 kv. and 200 to 400 ma.; for a dense compact breast free of fat, the kilovoltage is raised to 36 to 38, the other factors remaining constant. The obvious advantages of this technic, based on that used by Leborgne (15, 16) are demonstrated in Figures 1, 2, and 3. For the lateral views of the breast, a special cone is used. One sector is cut out so that, when the cone is in place, the cut-out sector allows compression of the breast between the film and cone without interference by the chest wall (Fig. 7). Shorter cones with smaller apertures are used for the spot-film technic. If the film can be brought close to the lesion in the breast, a film-target distance of 30 cm. is chosen; if the lesion cannot be placed close to the film, then a film-target distance of 75 cm. is used. Changes in film-target distance, necessitated by the apparatus and the thickness of the breast, must be compensated by appropriate changes in the milliamperage. The factors suggested for spot-film exposures are: 30 kv. and 25 ma. for each centimeter of tissue at 30 cm. film-target distance. Compression of the tumor-bearing portion of the breast can be effected by using a thin plastic sheet between the cone and the breast. If the tumor lies against the chest wall, gentle traction on the nipple will sometimes bring it forward into position for a good spot-film exposure.