Efficacy of computerized infrared imaging analysis to evaluate mammographically suspicious lesions.

OBJECTIVE: The purpose of this clinical trial was to determine the efficacy of a dynamic computerized infrared imaging system for distinguishing between benign and malignant lesions in patients undergoing biopsy on the basis of mammographic findings. SUBJECTS AND METHODS: A 4-year clinical trial was conducted at five institutions using infrared imaging of patients for whom breast biopsy had been recommended. The data from a blinded subject set were obtained in 769 subjects with 875 biopsied lesions resulting in 187 malignant and 688 benign findings. The infrared technique records a series of sequential images that provides an assessment of the infrared information in a mammographically identified area. The suspicious area is localized on the infrared image by the radiologist using mammograms, and an index of suspicion is determined, yielding a negative or positive result. RESULTS: In the 875 biopsied lesions, the index of suspicion resulted in a 97% sensitivity, a 14% specificity, a 95% negative predictive value, and a 24% positive predictive value. Lesions that were assessed as false-negative by infrared analysis were microcalcifications, so an additional analysis was performed in a subset excluding lesions described only as microcalcification. In this restricted subset of 448 subjects with 479 lesions and 110 malignancies, the index of suspicion resulted in a 99% sensitivity, an 18% specificity, a 99% negative predictive value, and a 27% positive predictive value. Analysis of infrared imaging performance in all 875 biopsied lesions revealed that specificity was statistically improved in dense breast tissue compared with fatty breast tissue. CONCLUSION: Infrared imaging offers a safe noninvasive procedure that would be valuable as an adjunct to mammography in determining whether a lesion is benign or malignant.

Mammographic density changes during the menstrual cycle.

The ability to detect small tumors is impaired in dense mammograms. It has been suggested that the sensitivity of mammograms could be lower in mammograms obtained during the luteal phase of the menstrual cycle. We examined the change in mammographic density from the follicular to the luteal phase of the menstrual cycle in 11 women. Although the average increase in densities was quite small (1.2%; P = 0.08), six women had clinically significant increases (1.4-7.8%), suggesting that premenopausal women should undergo mammographic examinations in the follicular part of the menstrual cycle.

CT cystography versus conventional cystography in evaluation of bladder injury.

OBJECTIVE: The objective of this study was to evaluate prospectively the use of CT cystography, using retrograde filling of the bladder with diluted iodinated contrast material, versus conventional cystography to identify bladder injury in patients with hematuria after blunt abdominal trauma. SUBJECTS AND METHODS: Inclusion criteria consisted of the adult hemodynamically stable abdominal trauma patient with hematuria referred for abdominopelvic CT and also being considered for cystography. An initial abdominopelvic CT scan using IV iodinated contrast material was obtained, as would have been done routinely in the trauma victim. A second CT scan through the pelvis was obtained after retrograde distention of the bladder with dilute iodinated contrast material. CT cystography revealing bladder injury was followed with appropriate therapy. CT cystograms not revealing injury were followed by conventional cystography. Results of patient outcome were evaluated. RESULTS: Over a 21-month period from January 1995 through September 1996, CT cystography was performed on 55 patients who presented with hematuria after blunt abdominal trauma. Five of the 55 patients had bladder injury on CT cystography. The injury in each of these five patients was confirmed intraoperatively. In the remaining 50 patients, both CT and conventional cystography did not reveal bladder injury. CONCLUSION: CT cystography is an accurate method for evaluating bladder injury in the blunt abdominal trauma victim with hematuria. CT cystography, performed in conjunction with routine CT of the abdomen and pelvis for evaluating traumatic hematuria, would therefore preclude conventional cystograms in these patients.

A multisite phase III study of the safety and efficacy of a new manganese chloride-based gastrointestinal contrast agent for MRI of the abdomen and pelvis.

The purpose of this study was to evaluate the safety and efficacy of a manganese chloride-based oral magnetic resonance (MR) contrast agent during a Phase III multisite clinical trial. Two hundred seventeen patients were enrolled who were already scheduled for MRI of the abdomen and/or pelvis. In this group of patients, it was postulated that the use of an oral agent would better allow discrimination of pathology from bowel. Patients with known gastrointestinal pathology including peptic ulcer disease, inflammatory bowel disease, obstruction, or perforation were excluded to minimize confounding variables that could affect the safety assessment. Of these 217 patients, 18 received up to 900 mL of placebo, and 199 patients were given up to 900 mL of a manganese chloride-based oral contrast agent, LumenHance (Bracco Diagnostics, Inc.). Safety was determined by comparing pre- and post-dose physical examinations, vital signs, and laboratory examinations and by documenting adverse events. Efficacy was assessed by unblinded site investigators and two blinded reviewers who compared pre- and post-dose T1- and T2-weighted MRI scans of the abdomen and/or pelvis. In 111 (57%) of the 195 cases evaluated for efficacy by site investigators (unblinded readers), MRI after LumenHance provided additional diagnostic information. Increased information was found by two blinded readers in 52% and 51% of patients, respectively. In 44/195 cases (23%) unblinded readers felt the additional information would have changed patient diagnosis and in 50 patients (26%), it would have changed management and/or therapy. Potential changes in patient diagnosis or management/therapy were seen by the two blinded readers in 8-20% of patients. No clinically significant post-dose laboratory changes were seen. Forty-eight patients (24%) receiving LumenHance and four patients (22%) receiving placebo experienced one or more adverse events. Gastrointestinal tract side effects were most common, seen in 29 (15%) of LumenHance patients and in 3 (17%) of the placebo patients. LumenHance is a safe and efficacious oral gastrointestinal contrast agent for MRI of the abdomen and pelvis.

The detection of changes in mammographic densities.

We previously reported reductions in mammographic densities in women participating in a trial of a gonadotropin-releasing hormone agonist (GnRHA)-based regimen for breast cancer prevention. In our previous report, we compared (by simultaneous evaluation) three basic elements of mammographic densities. The purpose of the present study was to evaluate whether a standard (expert) method of measuring mammographic densities would detect such changes in densities and whether a novel nonexpert computer-based threshold method could do so. Mammograms were obtained from 19 women at baseline and 12 months after randomization to the GnRHA-based regimen. The extent of mammographic densities was determined by: (a) a standard expert outlining method developed by Wolfe and his colleagues (Am. J. Roentgenol., 148: 1087-1092, 1987); and (b) a new computer-based threshold method of determining densities. The results from both the expert outlining method and the computer-based threshold method were highly consistent with the results of our original (simultaneous evaluation) method. All three methods yielded statistically significant reductions in densities from baseline to the 12-month follow-up mammogram in women on the contraceptive regimen. The difference between the treated and the control group was statistically significant with the expert outlining method and was of borderline statistical significance with the computer-based threshold method. The computer-based results correlated highly (r > 0.85) with the results from the expert outlining method. Both the standard expert outlining method and the computer-based threshold method detected the reductions we had previously noted in mammographic densities induced by the GnRHA-based regimen.

Management of complex urologic injuries.

The management of complex urologic trauma requires considerable experience and familiarity with reconstructive techniques. The goal should always be maximum preservation of normal function, with the fewest serious complications. Ideally these cases are treated by a multidisciplinary team rather than the trauma surgeon alone.

Gadoteridol-enhanced MR imaging of malignant hepatic tumors: effects of triple versus standard doses on lesion-liver contrast.

OBJECTIVE: The purpose of this study was to compare liver signal-to-noise ratio (SNR), lesion SNR, and lesion-liver contrast-to-noise-ratio (CNR) in patients with malignant liver lesions after the administration of a standard dose (0.1 mmol/kg of body weight) or a triple dose (0.3 mmol/kg) of a gadolinium chelate (gadoteridol). We hypothesized that the higher dose would produce a higher lesion-liver CNR and therefore increase the conspicuity of hepatic lesions. MATERIALS AND METHODS: A total of 85 patients with malignant hepatic masses (61 metastases, 22 hepatocellular carcinomas, and two lymphomas) proved by histologic or follow-up studies underwent MR imaging at 1.5 T. T1-weighted spin-echo imaging and gradient-echo imaging were done before and within 1 min after (gradient echo) as well as 5 (spin echo) and 15 (spin echo) min after the injection of 0.1 or 0.3 mmol of gadoteridol per kg, randomized before the start of the study (39 patients received the standard dose, and 46 received the triple dose). The signal intensities of the liver and lesions and the SD of background noise were measured by use of regions of interest to calculate the SNR of the liver and malignant lesions and the lesion-liver CNR. RESULTS: The lesion-liver CNR was increased significantly at 5 and 15 min after the administration of gadoteridol. No significant differences in the liver SNR, lesion SNR, and lesion-liver CNR (after 1 min: standard dose, -5 +/- 8, and triple dose, -4 +/- 14; after 5 min: standard dose, -1 +/- 5, and triple dose, 2 +/- 8; and after 15 min: standard dose, 1 +/- 5, and triple dose, 6 +/- 20) were found between the doses at all time points. CONCLUSION: Triple-dose gadoteridol does not improve the lesion-liver contrast of malignant hepatic lesions over that provided by the standard dose and is not warranted for liver MR imaging.

Cost-effective use of low-osmolality contrast media for CT of the liver: evaluation of liver enhancement provided by various doses of iohexol.

OBJECTIVE: Because of pending efforts to reform health care in the United States, judicious use of low-osmolality contrast media is important. We studied the effects of using various concentrations and volumes of iohexol, compared with the conventional dose and concentration of diatrizoate meglumine used for CT, to determine if a more cost-effective dose results in diagnostically efficacious liver enhancement. SUBJECTS AND METHODS: A total of 902 patients received one of nine different doses of IV contrast media. Eight doses of iohexol were used: 125 ml of iohexol 350 (350 mg l/ml, 44 g l/dose), 100 ml of iohexol 350 (35 g l/dose), 150 ml of iohexol 300 (300 mg l/ml, 45 g l/dose), 120 ml of iohexol 300 (36 g l/dose), 100 ml of iohexol 300 (30 g l/dose), 175 ml of iohexol 240 (240 mg l/ml, 42 g l/dose), 150 ml of iohexol 240 (36 g l/dose), and 125 ml of iohexol 240 (30 g l/dose). A single dose (150 ml) of diatrizoate meglumine 60% (w/v) was used (42 g l/dose). Contrast material was injected at a rate of 2 ml/sec. Scanning began 35-45 sec after injection. Quantitative analysis of enhancement was performed by obtaining region-of-interest measurements through the liver on scans obtained before and after injection of contrast material. Mean and maximum changes in hepatic density and mean time to maximum enhancement were measured. Mean time-density curves were subsequently derived for each dose of contrast material. Qualitative analysis of enhancement was performed by using subjective, previously defined criteria. All studies were interpreted in a double-blind fashion. RESULTS: Mean hepatic enhancement was greater with 125 ml of iohexol 350 and 150 ml of iohexol 300 than with other doses of contrast material (p < .05). Both 125 ml of iohexol 350 and 150 ml of iohexol 300 produced actual hepatic enhancement of more than 50 H for over 60 sec. The greatest maximum increase in hepatic density occurred with 125 ml of iohexol 350. When analyzed qualitatively, 150 ml of iohexol 300 resulted in the highest percentage of optimum enhancement. CONCLUSION: According to quantitative analysis, 125 ml of iohexol 350 administered at a rate of 2 ml/sec produces the best enhancement, whereas according to qualitative analysis, 150 ml of iohexol 300 produces the best enhancement. All doses of iohexol 240 provide poor enhancement compared with a conventional dose of contrast material of 150 ml of diatrizoate meglumine 60% or 150 ml of iohexol 300. A moderate cost savings can be achieved by using 125 ml of iohexol 350 for dynamic sequential CT.

Changes in mammographic densities induced by a hormonal contraceptive designed to reduce breast cancer risk.

BACKGROUND: It has been known for some time that oral contraceptives substantially reduce the risk of endometrial and ovarian cancer, but they do not reduce the risk of breast cancer. A hormonal contraceptive regimen has been developed which uses a gonadotropin-releasing hormone against (GnRHA) to suppress ovarian function, and this regimen includes the administration of very low doses of both estrogen and progestogen. This hormonal contraceptive regimen attempts to minimize exposure of the breast epithelium to these steroids and to preserve the maximum beneficial effects of estrogen, while still preventing endometrial hyperplasia. PURPOSE: Our purpose was to determine whether changes occurred in mammographic densities between baseline and 1 year for women on this hormonal contraceptive regimen with reduced estrogen and progestogen levels compared with women in a control group. METHODS: Twenty-one women were randomly assigned in a 2:1 ratio to the GnRHA-based contraceptive group (14 women) or to a control group (seven women). The contraceptive group received the following: 7.5 mg leuprolide acetate depot by intramuscular injection every 28 days; 0.625 mg conjugated estrogen by mouth for 6 days out of 7 every week; and 10 mg medroxyprogesterone acetate orally for 13 days every fourth 28-day cycle. The control group received no medication. Baseline and 1-year follow-up mammograms of contraceptive and control subjects were reviewed in a blinded fashion by two radiologists. RESULTS: Comparison of the changes between the baseline and 1-year mammograms in the two groups of women showed significant (P = .039) reduction in mammographic densities at 1 year for women on the contraceptive regimen. Assessing the reduction in mammographic densities by noting the fineness of fibrous septae showed a highly significant (P = .0048) difference in the contraceptive regimen group. One of the women on the contraceptive regimen was withdrawn from the study because of poor compliance. CONCLUSION: The reduced estrogen and progestogen exposures to the breast that were achieved by the hormonal contraceptive regimen resulted in substantial reductions in follow-up mammographic densities at 1 year compared with baseline. Although there is no direct evidence that such a reduction in densities will lead to a reduced risk of breast cancer, indirect evidence for a protective effect of this regimen is that early menopause reduces breast cancer risk, and that menopause is associated with a reduction in mammographic densities.

PIP: In California, physicians randomly assigned 21 women aged 25-40 to either the contraceptive group or the control group as part of a study aimed to determine whether or not a hormonal contraceptive regimen with reduced estrogen and progestogen levels affects mammographic densities. Eligibility criteria included premenopausal women with a 5-fold greater than normal risk of breast cancer, no prior cancer, bone mineral density not less than 2 standard deviations below normal, normal cholesterol, and a normal physical and pelvic examination. The contraceptive group received intramuscular injection of 7.5 mg leuprolide acetate depot every 28 days, 0.625 mg oral conjugated estrogen for 6 out of 7 days every week, and 10 mg oral medroxyprogesterone acetate for 13 days every fourth 28-day cycle. The reduction in mammographic densities in women on the contraceptive regimen between baseline and 1 year was significantly different than that of the controls whose mammographic densities remained essentially the same (p = 0.039). Cases had significantly more change in fibrous septae between baseline and 1 year than did controls (+0.82 units vs. -0.07; p = 0.0048). These results indicate that lower levels of estrogen and progestogen reduces mammographic densities, which may reduce the risk of breast cancer since increased mammographic densities are linked to an increased risk of breast cancer. Reduced mitotic activity in breast epithelial cells during menopause and with lower levels of estrogen and progestogen (i.e., reduced mammographic densities) suggest that early menopause may also protect against breast cancer.