Validation of a power-law noise model for simulating small-scale breast tissue.

We have validated a small-scale breast tissue model based on power-law noise. A set of 110 patient images served as truth. The statistical model parameters were determined by matching the radially averaged power-spectrum of the projected simulated tissue with that of the central tomosynthesis patient breast projections. Observer performance in a signal-known exactly detection task in simulated and actual breast backgrounds was compared. Observers included human readers, a pre-whitening observer model and a channelized Hotelling observer model. For all observers, good agreement between performance in the simulated and actual backgrounds was found, both in the tomosynthesis central projections and the reconstructed images. This tissue model can be used for breast x-ray imaging system optimization. The complete statistical description of the model is provided.

Immune reconstitution renal-limited sarcoidosis presenting as acute kidney injury.

An HIV-infected asymptomatic woman developed acute kidney injury six weeks after initiation of combination antiretroviral therapy (cART). A renal biopsy revealed both renal-limited sarcoidosis and HIV nephropathy. The acute renal injury reversed with glucocorticoid therapy.

Automated detection of mass lesions in dedicated breast CT: a preliminary study.

PURPOSE: To develop an automated method to detect breast masses on dedicated breast CT (BCT) volumes and to conduct a preliminary evaluation of its performance. This method can be used in a computer-aided detection (CADe) system for noncontrast enhanced BCT. METHODS: The database included patient images, which were acquired under an IRB-approved protocol. The database in this study consisted of 132 cases. 50 cases contained 58 malignant masses, and 23 cases contained 24 benign masses. 59 cases did not contain any biopsy-proven lesions. Each case consisted of an unenhanced CT volume of a single breast. First, each breast was segmented into adipose and glandular tissues using a fuzzy c-means clustering algorithm. The glandular breast regions were then sampled at a resolution of 2 mm. At each sampling step, a 3.5-cm(3) volume-of-interest was subjected to constrained region segmentation and 17 characteristic features were extracted, yielding 17 corresponding feature volumes. Four features were selected using step-wise feature selection and merged with linear discriminant analysis trained in the task of distinguishing between normal breast glandular regions and masses. Detection performance was measured using free-response receiver operating characteristic analysis (FROC) with leave-one-case-out evaluation. RESULTS: The feature selection stage selected features that characterized the shape and margin strength of the segmented region. CADe sensitivity per case was 84% (std = 4.2%) at 2.6 (std = 0.06) false positives per volume, or 6 × 10(-3) per slice (at an average of 424 slices per volume in this data set). CONCLUSIONS: This preliminary study demonstrates the feasibility of our approach for CADe for BCT.

On the orientation of mammographic structure.

PURPOSE: Burgess et al. have shown that the power-spectral density of mammographic breast tissue P(f) follows a power-law, P(f) = c∕f(ß).(1) Due to the complexity of the breast anatomy, breast phantoms often make use of power-law backgrounds to approximate the irregular texture of breast images. However, the current methodology of estimating power-law coefficients assumes that the breast structure is isotropic. The purpose of this letter is to demonstrate that breast anatomic structure is not isotropic, but in fact has a preferred orientation. Further, we present a formalism to estimate power-law coefficients ß and c while accounting for tissue orientation in mammographic regions-of-interests (ROIs). We then show the effect of structure orientation on ß and c, as well as on the appearance of simulated power-law backgrounds. METHODS: When breast tissue exhibits a preferred orientation, the radial symmetry in the associated power spectrum is broken. The new symmetry was fit by an ellipsoidal model. Ellipse tilt angle and axis ratio were accounted for in the power-law fit. RESULTS: On average, breast structure was found to point toward the nipple: the average orientation in MLO views was 22.5 °, while it was 5 ° for CC views, and the mean orientation for left breasts was negative while it was positive for right breasts. For both power-law magnitude and exponent, the mean difference was statistically significant (<Δß > = -0.096, <Δlog(c) > =-0.192). CONCLUSIONS: A formalism for quantification of breast structure and structure orientation is provided. The difference in power-law coefficient estimates when accounting for orientation was found to be statistically significant. Examples of statistically defined backgrounds indicate that breast structure is mimicked more closely when structure orientation is accounted for.

Task-based assessment of breast tomosynthesis: effect of acquisition parameters and quantum noise.

PURPOSE: Tomosynthesis is a promising modality for breast imaging. The appearance of the tomosynthesis reconstructed image is greatly affected by the choice of acquisition and reconstruction parameters. The purpose of this study was to investigate the limitations of tomosynthesis breast imaging due to scan parameters and quantum noise. Tomosynthesis image quality was assessed based on performance of a mathematical observer model in a signal-known exactly (SKE) detection task. METHODS: SKE detectability (d') was estimated using a prewhitening observer model. Structured breast background was simulated using filtered noise. Detectability was estimated for designer nodules ranging from 0.05 to 0.8 cm in diameter. Tomosynthesis slices were reconstructed using iterative maximum-likelihood expectation-maximization. The tomosynthesis scan angle was varied between 15 degrees and 60 degrees, the number of views between 11 and 41 and the total number of x-ray quanta was infinity, 6 X 10(5), and 6 x 10(4). Detectability in tomosynthesis was compared to that in a single projection. RESULTS: For constant angular sampling distance, increasing the angular scan range increased detectability for all signal sizes. Large-scale signals were little affected by quantum noise or angular sampling. For small-scale signals, quantum noise and insufficient angular sampling degraded detectability. At high quantum noise levels, angular step size of 3 degrees or below was sufficient to avoid image degradation. At lower quantum noise levels, increased angular sampling always resulted in increased detectability. The ratio of detectability in the tomosynthesis slice to that in a single projection exhibited a peak that shifted to larger signal sizes when the angular range increased. For a given angular range, the peak shifted toward smaller signals when the number of views was increased. The ratio was greater than unity for all conditions evaluated. CONCLUSION: The effect of acquisition parameters on lesion detectability depends on signal size. Tomosynthesis scan angle had an effect on detectability for all signals sizes, while quantum noise and angular sampling only affected the detectability small-scale signals.

Automated detection of microcalcification clusters for digital breast tomosynthesis using projection data only: a preliminary study.

Digital breast tomosynthesis (DBT) is a promising modality for breast imaging in which an anisotropic volume image of the breast is obtained. We present an algorithm for computerized detection of microcalcification clusters (MCCs) for DBT. This algorithm operates on the projection views only. Therefore it does not depend on reconstruction, and is computationally efficient. The algorithm was developed using a database of 30 image sets with microcalcifications, and a control group of 30 image sets without visible findings. The patient data were acquired on the first DBT prototype at Massachusetts General Hospital. Algorithm sensitivity was estimated to be 0.86 at 1.3 false positive clusters, which is below that of current MCC detection algorithms for full-field digital mammography. Because of the small number of patient cases, algorithm parameters were not optimized and one linear classifier was used. An actual limitation of our approach may be that the signal-to-noise ratio in the projection images is too low for microcalcification detection. Furthermore, the database consisted of predominantly small MCC. This may be related to the image quality obtained with this first prototype.

Computerized mass detection for digital breast tomosynthesis directly from the projection images.

Digital breast tomosynthesis (DBT) has recently emerged as a new and promising three-dimensional modality in breast imaging. In DBT, the breast volume is reconstructed from 11 projection images, taken at source angles equally spaced over an arc of 50 degrees. Reconstruction algorithms for this modality are not fully optimized yet. Because computerized lesion detection in the reconstructed breast volume will be affected by the reconstruction technique, we are developing a novel mass detection algorithm that operates instead on the set of raw projection images. Mass detection is done in three stages. First, lesion candidates are obtained for each projection image separately, using a mass detection algorithm that was initially developed for screen-film mammography. Second, the locations of a lesion candidate are backprojected into the breast volume. In this feature volume, voxel intensities are a combined measure of detection frequency (e.g., the number of projections in which a given lesion candidate was detected), and a measure of the angular range over which a given lesion was detected. Third, features are extracted after reprojecting the three-dimensional (3-D) locations of lesion candidates into projection images. Features are combined using linear discriminant analysis. The database used to test the algorithm consisted of 21 mass cases (13 malignant, 8 benign) and 15 cases without mass lesions. Based on this database, the algorithm yielded a sensitivity of 90% at 1.5 false positives per breast volume. Algorithm performance is positively biased because this dataset was used for development, training, and testing, and because the number of algorithm parameters was approximately the same as the number.of patient cases. Our results indicate that computerized mass detection in the sequence of projection images for DBT may be effective despite the higher noise level in those images.

Computerized detection of mass lesions in digital breast tomosynthesis images using two- and three dimensional radial gradient index segmentation.

Initial results for a computerized mass lesion detection scheme for digital breast tomosynthesis (DBT) images are presented. The algorithm uses a radial gradient index feature for the initial lesion detection and for segmentation of lesion candidates. A set of features is extracted for each segmented partition. Performance of two- and three dimensional features was compared. For gradient features, the additional dimension provided no improvement in classification performance. For shape features, classification using 3D features was improved compared to the 2D equivalent features. The preliminary overall performance was 76% sensitivity at 11 false positives per exam, estimated based on DBT image data of 21 masses. A larger database will allow for further development and improvement in our computer aided detection scheme.

Idiopathic polymyositis and glomerulonephritis.

We report a 28-year-old male who presented with a clinical picture compatible with idiopathic polymyositis and nephrotic-range proteinuria. Muscle biopsy confirmed the diagnosis of polymyositis and a diagnostic renal biopsy demonstrated IgM mesangial glomerulonephritis. Following a short-course of prednisone, both the myositis and proteinuria resolved. Glomerulonephritis associated with idiopathic polymyositis is rare; however, since it appeared to respond to corticosteroid therapy concomitant with the improvement in the myositis, it was likely an associated immunological complication.

Aging and urinary excretion of epidermal growth factor.

The aging process in man leads to some loss of kidney mass and function. The kidney produces epidermal growth factor (EGF), a polypeptide involved in the repairing process of epithelial cells. Human urine contains high concentrations of EGF, derived from its production in the kidney. It is not known if aging alters urinary EGF production in humans. This study investigates the possibility of decreased urinary EGF in elderly people. Urine samples were collected from 70 healthy subjects of various ages and measured for EGF by the technique of radioimmunoassay. The studied urine samples were divided into five age groups (3 to 10, 11 to 20, 21 to 60, 61 to 70, and 71 to 80 years). Urinary EGF (corrected for the urine creatinine concentration and measured as ng per mg creatinine) was highest in the two youngest groups, 78.5 +/- 14.3 and 76.2 +/- 18.8 (mean +/- standard error of the mean), respectively, and decreased with age so that the lowest urinary EGF was observed in the oldest group (27.0 +/- 8.8 ng per mg creatinine). In addition, a significant inverse relationship exists between urinary EGFD in all 79 subjects and their respective age (P < 0.001). These findings show that normal values of urinary EGF should take age into account. The reduced production of EGF by the kidney in the elderly may have functional significance in retarding the repair process in the kidney.

Reversal of trimethoprim-induced antikaliuresis.

High-dose trimethoprim-sulfamethoxazole (TMP-SMX) causes hyperkalemia, thought to result from TMP-induced blockade of amiloride-sensitive Na(+)-channels in the distal nephron. The present study was performed in anesthetized dogs to determine if increasing distal sodium delivery affects this antikaliuretic effect. In Group 1, intrarenal infusion of vehicle did not alter renal function. In Group 2, i.v. infusion of amiloride led to diuresis, natriuresis and antikaliuresis associated with a reduction of the transtubular potassium gradient (TTKG) in both kidneys. Intrarenal infusion of TMP (0.2 mg/kg/min) into the left kidney did not further alter these parameters. In groups 3 and 4, intrarenal infusion of TMP caused an ipsilateral diuresis, natriuresis, antikaliuresis and a reduction in (TTKG) without affecting the contralateral kidney. The TMP infusion was followed by furosemide (20 mg i.v.) in group 3 and acute saline loading in group 4. Despite continuous TMP infusion, both furosemide and saline loading reversed the antikaliuretic effect of TMP in the ipsilateral kidney and was associated with a similar kaliuresis, diuresis, natriuresis and decrease in urine osmolality in both kidneys. The TTKG following furosemide or saline loading increased in the ipsilateral kidney and decreased in the contralateral kidney. In all groups the systemic and renal hemodynamics remained unchanged. These results suggest that acute administration of TMP inhibits the amiloride-sensitive Na(+)-channel and K+ secretion in the distal nephron. Maneuvers that increase distal Na+ delivery can abrogate TMP's antikaliuretic effect due, in part, to an increase of the low TTKG observed with TMP.

Hyperkalemia with high-dose trimethoprim-sulfamethoxazole therapy.

In a patient with the acquired immunodeficiency syndrome, a progressive increase in the serum potassium concentration occurred with high-dose trimethoprim-sulfamethoxazole (TMP-SMX) therapy for Pneumocystis carinii pneumonia. In this patient, factors known to alter transcellular potassium shifts to induce hyperkalemia were not present. There was no evidence of glucocorticoid or mineralocorticoid insufficiency at the time of hyperkalemia, while the transtubular potassium gradient decreased. The hyperkalemia resolved spontaneously on discontinuation of TMP-SMX therapy, suggesting that this electrolyte abnormality is related to altered renal tubular secretion of potassium as a consequence of the high-dose TMP-SMX therapy.

Trimethoprim-sulfamethoxazole induces reversible hyperkalemia.

OBJECTIVE: To determine the effect of trimethoprimsulfamethoxazole (Tmp-Smx) on serum potassium concentration. DESIGN: Retrospective cohort study. SETTING: An urban teaching hospital. PATIENTS: Fifty-one persons hospitalized for symptomatic infection with human immunodeficiency virus (HIV). Twenty-five patients who were taking high-dose Tmp-Smx (trimethoprim 20 mg/kg per day; sulfamethoxazole, 100 mg/kg per day) for Pneumocystis carinii pneumonia were the study group. Twenty-six patients who had not received the drug were the control group. Patients who received potassium supplements, those taking medications known to alter potassium homeostasis or renal function, or those with a serum creatinine level more than 186 mumol/L were excluded. MEASUREMENTS AND MAIN RESULTS: Serum potassium concentration in the study group was 4.1 +/- 0.1 mmol/L (mean +/- SE) and increased by 1.1 mmol/L (Cl, 0.8 to 1.5 mmol/L) (P < 0.0001) 9.8 +/- 0.5 days after starting Tmp-Smx therapy. Patients followed longitudinally showed a progressive increase in serum potassium levels during therapy and a progressive decline after discontinuing Tmp-Smx. Blood urea nitrogen and serum creatinine levels increased mildly from 4.3 +/- 0.5 mmol/L and 85 +/- 6 mumol/L to 6.4 +/- 0.7 mmol/L and 113 +/- 8 mumol/L, respectively. The serum potassium level in the control group was 4.3 +/- 0.1 mmol/L and remained unchanged during hospitalization. CONCLUSIONS: High-dose Tmp-Smx therapy used for the treatment of P. carinii pneumonia in HIV-infected patients leads to an increase in the serum potassium concentration and may result in life-threatening hyperkalemia. Patients receiving high doses of Tmp-Smx require close monitoring of their serum potassium concentration, particularly 7 to 10 days after the start of therapy.

Reversal of Na+ retention in chronic caval dogs by verapamil: contribution of medullary circulation.

The effects of verapamil on papillary plasma flow (PPF) and Na+ excretion were studied in anesthetized chronic caval dogs with low cardiac output and Na+ retention. Infusion of verapamil into the left renal artery (5 and 10 micrograms.kg-1.min-1) caused a dose-dependent ipsilateral increase in renal blood flow and Na+ excretion (from 10 +/- 2 to 171 +/- 32 and 225 +/- 35 mu eq/min, respectively). PPF in the left kidney was 26.6 +/- 4.4 and was significantly greater than that measured in the contralateral kidney (13.3 +/- 2.4 ml.min-1.100 g-1) (P < 0.01). The natriuresis occurred independent of changes in cardiac output and peripheral vascular resistance. In a separate group of caval dogs in which stimulation of the renin-angiotensin and adrenergic systems was intensified with a tighter caval constriction, verapamil failed to induce renal vasodilation or natriuresis and PPF was not altered. Despite the disparate hemodynamic responses, verapamil stimulated renal production of both renin and prostaglandin E2 in both groups of caval dogs. We conclude that the ability of verapamil to induce papillary vasodilation may contribute to the natriuresis seen in the caval dog, in which the site of Na+ retention includes the loop of Henle.

Failure of atrial natriuretic peptide to induce natriuresis in aortocaval fistula dogs.

Creation of an aortocaval fistula (ACF) in dogs induces salt and water retention, activation of the renin-angiotensin and adrenergic nervous systems and renal papillary ischemia associated with high levels of circulating atrial natriuretic peptide (ANP). The effects of intrarenal ANP (1.2 micrograms/min) infusion on systemic and renal hemodynamics, renal excretory function, renal output of renin and norepinephrine (NE) and papillary plasma flow (PPF) were studied in both normal and ACF dogs. ANP did not alter systemic hemodynamics in either group, but led to a significant increase in renal blood flow (RBF), glomerular filtration rate (GFR), urine flow rate (V), sodium excretion (UNaV) and fractional excretion of sodium (FENa), and a significant decrease in renal vascular resistance (RVR) and urine osmolality (UOsm) in normal dogs. GFR, RBF, RVR, V, UNaV, FENa and UOsm remained unchanged, however, in ACF dogs. In ACF dogs, both renal renin and NE output were significantly greater during baseline and remained significantly greater following ANP infusion, associated with a significantly lower PPF compared with normal dogs. These data suggest that ACF dogs are resistant to the renal effects of ANP, which can neither mitigate the hormonal mediators of sodium retention nor reverse the papillary ischemia observed in this model.

The incidence and epidemiology of human immunodeficiency virus infection in 320 patients treated in an inner-city hemodialysis center.

From January 1, 1986 through June 30, 1989, 320 maintenance hemodialysis patients treated at The Brookdale Hospital Medical Center were tested for the presence of antibody to the human immunodeficiency virus (HIV) using the enzyme-linked immunosorbent assay (ELISA) and Western blot assays. Thirty-nine patients (12%) tested positive for HIV antibody (HIV+) with both the ELISA and Western blot, 24 (62%) of whom were known intravenous drug abusers (IVDA). Of the remaining non-IVDA patients, unanticipated HIV+ results were found in 10 (25%). Thirty-four (87%) of the 39 HIV+ patients were asymptomatic at the start of the study, while two had acquired immunodeficiency syndrome (AIDS) and three others, AIDS-related complex (ARC). Four patients subsequently developed AIDS 20 +/- 4.9 weeks (range, 12 to 32) after testing, three of whom initially had ARC. One patient developed ARC 7 months after testing. Sixteen HIV+ patients died, including five of the six with AIDS, one with ARC, and two others from Mycobacterium tuberculosis. The eight other deaths were from causes unrelated to HIV disease and occurred 12 +/- 2.3 months (range, 1 to 24) after testing. Two HIV+ patients were lost to follow-up. Twenty-one HIV+ patients (54%) are alive and 20 (51%) asymptomatic 15 +/- 2.4 months (range, 1 to 42) after HIV testing. Thus, despite HIV positivity, 28 patients (72%) had an asymptomatic period lasting 14 +/- 1.9 months (range, 1 to 42). Seventy-two of the 281 HIV-negative (HIV-) patients died during the study. None of the HIV- patients manifested ARC or AIDS, confirming that there was no false-negative HIV test.(ABSTRACT TRUNCATED AT 250 WORDS)

Minoxidil, nadolol, and a diuretic. Once-a-day therapy for resistant hypertension.

We tested a once-a-day antihypertensive regimen using minoxidil, nadolol, and a diuretic in 55 patients with resistant hypertension. Forty-seven patients had evidence of end-organ damage. Twelve had mild renal insufficiency (serum creatinine concentration, 2.5 +/- 0.3 mg/dL). In 34 patients, treatment with nadolol and a diuretic was started with minoxidil added one to four weeks later. In the remainder, minoxidil, nadolol, and a diuretic were begun simultaneously because of severe hypertension. Initial supine and standing blood pressure (BP) in the 55 patients were 186 +/- 4/111 +/- 2 and 180 +/- 4/108 +/- 2 mm Hg, respectively. After 7 +/- 1 weeks, BP was controlled in 46 patients (84%) with the supine and standing BP reduced to 140 +/- 3/80 +/- 1 and 134 +/- 3/80 +/- 1, respectively. In six patients, BP was controlled but intolerable side effects occurred, making the regimen therapeutically successful in 40 patients (73%). The BP remained controlled during a follow-up of 43 +/- 5 weeks. In 31 patients, BPs measured 24 hours after the last dose were not different from random measurements. Mean serum creatinine levels remained stable in the 12 patients with renal insufficiency.