Effects of perfluorochemical distribution and elimination dynamics on cardiopulmonary function.

Based on a physicochemical property profile, we tested the hypothesis that different perfluorochemical (PFC) liquids may have distinct effects on intrapulmonary PFC distribution, lung function, and PFC elimination kinetics during partial liquid ventilation (PLV). Young rabbits were studied in five groups [healthy, PLV with perflubron (PFB) or with perfluorodecalin (DEC); saline lavage injury and conventional mechanical ventilation (CMV); saline lavage injury PLV with PFB or with DEC]. Arterial blood chemistry, respiratory compliance (Cr), quantitative computed tomography of PFC distribution, and PFC loss rate were assessed for 4 h. Initial distribution of PFB was more homogenous than that of DEC; over time, PFB redistributed to dependent regions whereas DEC distribution was relatively constant. PFC loss rate decreased over time in all groups, was higher with DEC than PFB, and was lower with injury. In healthy animals, arterial PO(2) (Pa(O(2))) and Cr decreased with either PFC; the decrease was greater and sustained with DEC. Lavaged animals treated with either PFC demonstrated increased Pa(O(2)), which was sustained with PFB but deteriorated with DEC. Lavaged animals treated with PFB demonstrated increased Cr, higher Pa(O(2)), and lower arterial PCO(2) than with CMV or PLV with DEC. The results indicate that 1) initial distribution and subsequent intrapulmonary redistribution of PFC are related to PFC properties; 2) PFC distribution influences PFC elimination, gas exchange, and Cr; and 3) PFC elimination, gas exchange, and Cr are influenced by PFC properties and lung condition.

Carcinogenesis and the plasma membrane.

Presented is a two-stage hypothesis of carcinogenesis based on: (1) plasma membrane defects that produce abnormal electron and proton efflux; and (2) electrical uncoupling of cells through loss of intercellular communication. These changes can be induced by a wide variety of stimuli including chemical carcinogens, oncoviruses, inherited and/or acquired genetic defects, and epigenetic abnormalities. The resulting loss of electron/proton homeostasis leads to decreased transmembrane potential, electrical microenvironment alterations, decreased extracellular pH, and increased intracellular pH. This produces a positive feedback loop to enhance and sustain the proton/electron efflux and loss of intercellular communication. Low transmembrane potential is functionally related to rapid cell cycling, changes in membrane structure, and malignancy. Intracellular alkalinization affects a variety of pH-sensitive systems including glycolysis, DNA synthesis, DNA transcription and DNA repair, and promotes genetic instability, accounting for the accumulation of genetic defects seen in malignancy. The abnormal microenvironment results in the selective survival and proliferation of malignant cells at the expense of contiguous normal cell populations.

Effect of single versus multiple dosing on perfluorochemical distribution and elimination during partial liquid ventilation.

The objective of this study was to quantitate perfluorochemical (PFC) elimination kinetics during partial liquid ventilation (PLV) following an initial fill with or without hourly dosing. Young New Zealand rabbits were studied in two groups: Gr I (n = 6), PLV with a single dose of PFC liquid (perflubron: LiquiVent, Alliance Pharmaceutical Corp.); and Gr II (n = 5), PLV with PFC liquid and multiple hourly dosing . All rabbits were studied for 4 h, following initial instillation of a volume of PFC liquid equal to the measured gas functional residual capacity. Animals were ventilated at a constant breathing frequency (30 br/min), tidal volume (9.3+/-0.3 SE mL/kg), positive end expiratory pressure (4 cm H2O), and inspiratory time (0.30 s). PFC saturation of mixed expired gas (PFC-Sat) was assessed with a thermal conductivity analyzer, and PFC elimination was calculated from PFC-Sat, minute ventilation, and temperature of the expired gas. In GR II, PFC was supplemented hourly at a volume determined by PFC elimination calculations. The results demonstrated a decrease in PFC-sat and PFC loss with time, independent of group (P< 0.05). In addition, with hourly supplementation (GR II), PFC-Sat and PFC elimination over time was significantly (P < 0.05) greater than in animals (GR I) which did not receive additional doses. These data demonstrate that the PFC elimination rate is not constant and is related to the amount of PFC in the respiratory system. This may have occurred due to distributional differences of ventilation and PFC liquid between the single and multiple dosing groups. These findings also suggest that evaluation of PFC concentrations in expired gas may be a clinically useful index of intrapulmonary PFC distribution during PLV, and that maintained elevation of expired gas PFC saturation may guide optimal PFC dosing intervals and distribution to maximize protection against barotrauma.

Clinical significance of increased density in the proximal femoral marrow detected by visual inspection on abdominopelvic postcontrast CT examination.

PURPOSE: The purpose of this study was to ascertain the clinical significance of increased density of the proximal femoral diaphyseal marrow when incidentally detected on postcontrast abdominopelvic CT examinations. METHOD: The proximal femoral marrow of 63 patients was classified as normal or abnormal based on visual inspection by three attending radiologists. Abnormal density was defined as attenuation greater than that of adjacent musculature. The attenuation of the marrow was also measured. All patient medical records were reviewed for pertinent laboratory and clinical data. RESULTS: Increased marrow density had a low sensitivity for anemia (28%) but a high specificity and positive predictive value (100%) for anemia. Three of these patients had unilaterally increased attenuation associated with local pathology. Visual inspection was adequate for identifying abnormalities in instances of underlying malignancy. CONCLUSION: Increased density of the proximal femoral diaphysis is a highly specific finding for a marrow replacement process. Anemia was the most common clinical diagnosis in our series of patients with abnormal marrow density. Although the sensitivity for increased bone marrow attenuation is low, the extremely high specificity and positive predictive value of this finding for marrow reconversion and/or replacement suggest that even if detected incidentally, it should not be disregarded and, in the absence of a preexisting causative diagnosis, warrants further evaluation. The specific pattern of marrow abnormality may be helpful in differentiating localized processes from other processes that may affect hematopoietic function in a more widespread or global distribution. In particular, visual inspection of marrow density was more specific for identifying asymmetric marrow density in localized processes than was a quantitative measure of difference between the two femurs (>20 HU).

MR appearance of uterine dehiscence in the post-cesarean section patient.

PURPOSE: CT has been shown to be unreliable for detecting uterine dehiscence in the postoperative period after cesarean section (c-section). The purpose of this investigation is to describe the MR appearance of uterine dehiscence in this setting and identify features that distinguish complete from partial dehiscence. METHOD: Over an 82 month period, all charts and MR reports of patients that underwent MRI of the pelvis after c-section were reviewed for uterine dehiscence. Altogether, 55 patients were imaged. Positive cases for dehiscence were retrospectively reviewed by two radiologists. Imaging criteria for complete dehiscence consisted of transmural disruption. Criteria for partial dehiscence consisted of disruption of the endometrial and/or serosal layer, without transmural extension. RESULTS: On MRI, five patients demonstrated abnormalities suggestive of incisional dehiscence. Based on these imaging criteria, two of these showed complete dehiscence that was proven at surgery and three showed findings of partial dehiscence. The optimal imaging plane was perpendicular to the incision. CONCLUSION: MR features may be utilized to identify total uterine dehiscence and may be more effective than CT.

Virtual bronchoscopy with perfluoronated hydrocarbon enhancement.

RATIONALE AND OBJECTIVES: Bronchoscopic computed tomography (CT) is limited by machine resolution and air-soft-tissue contrast. The objective of this study was to determine whether improving the contrast by using the contrast agent perflubron (PFOB) in the lung would improve the bronchoscopic CT technique and permit visualization of small airways. MATERIALS AND METHODS: Bronchoscopic CT was performed in an anesthetized 8-week-old New Zealand white rabbit before and after the endotracheal administration of PFOB. RESULTS: Bronchoscopic CT performed with PFOB permitted navigation of bronchi as small as 0.8 mm in diameter, which are much smaller than those that can be navigated without PFOB. CONCLUSION: In this example, the use of perfluorochemicals with bronchoscopic CT enhanced the capabilities of virtual bronchoscopy.

Nuclear oncology and the Imagene concept.

Over the past 2 decades we have witnessed an explosion of new radioisotopic tracers aimed at detecting, staging and eventually treating tumors. In fact, nuclear oncology has evolved into a field on its own. Aside from aspecific radioisotopic tracers such as thallium 201 or gallium 67, clinicians and oncologists can now use specific radiolabeled monoclonal antibodies and metabolic tracers. In the near future, molecular probes based on the sequencing of the human genome with an exquisite specificity should also become available. In this article, we shall review the most recent developments in this new field.

Signal characteristics of tumors shown by high-resolution endorectal coil magnetic resonance imaging may predict outcome among patients with cervical carcinoma treated with irradiation. A preliminary study.

BACKGROUND: The purpose of this study was to evaluate the role of high-resolution magnetic resonance imaging with the endorectal coil (eMRI) in the management of cervical carcinoma treated with definitive irradiation. METHODS: Eighteen patients with invasive cervical carcinoma (International Federation of Gynecology and Obstetrics Stages Ib-IIIb) consented to evaluation with eMRI on a 1.5 tesla system with high resolution (400 x 400 microM). Images were read to provide staging information and to grade the signal characteristics of the individual tumors as low (dark), intermediate, or high (bright) relative to surrounding isointense fat. Patients were treated with standard megavoltage irradiation (prescribed dose, 80-85 Gray); shaped antero-posterior/postero-anterior or 4-field box techniques, plus brachytherapy, were used. RESULTS: In 39% of patients, tumors were determined to be in a higher stage by eMRI because of proximal vaginal involvement (n = 4) or the combination of proximal vaginal involvement and parametrial extension (n = 3). Features predictive of improved local control and survival without evidence of disease included stage, hemoglobin levels > or = 11, complete response to external irradiation, and bright signal characteristics. Compared with those who had dark and/or intermediate tumors, patients who had tumors with bright signal characteristics tended to present with earlier stage disease, were less likely to have anemia, and were more likely to have complete response to external irradiation. CONCLUSIONS: Prognostic information for clinical staging of cervical carcinoma was contributed by eMRI. The technique was more likely to suggest proximal vaginal involvement by a tumor than was examination under anesthesia. Signal characteristics of tumors may provide valuable predictive information that is supplementary to conventional discriminants of outcome that follow definitive irradiation. Such information could allow physicians to tailor treatment (e.g., by the addition of radiation sensitizers) at an earlier point in disease management.

Rectal carcinoma: staging at MR imaging with endorectal surface coil. Work in progress.

To increase the accuracy of local staging of rectal carcinomas at magnetic resonance (MR) imaging, the authors placed on endorectal coil mounted on a balloon in a position adjacent to the lesion. Use of such a local coil resulted in increased signal-to-noise ratio compared with use of a body coil; higher-resolution images were obtained because the field of view was decreased. The depth of wall invasion by rectal carcinoma was correctly staged with endorectal MR imaging in 11 of 12 patients. In the detection of perirectal adenopathy, use of MR enabled correct identification of positive perirectal nodes in four of seven patients (57%). There were no false-positive diagnoses of perirectal adenopathy at MR. Endorectal MR imaging is an evolving and promising technique for the local staging of rectal carcinomas, but further studies are needed to demonstrate its efficacy.

Differential diagnosis of hepatic neoplasms: spin echo versus gadolinium-diethylenetriaminepentaacetate-enhanced gradient echo imaging.

Early results are reported of hepatic neoplasms studied with dynamic gadolinium-diethylenetriaminepentaacetate (Gd-DTPA)-enhanced magnetic resonance imaging (MRI). The purpose of this study was to evaluate the potential of the Gd enhancement pattern for characterizing these neoplasms and to compare the performance of spin-echo (SE) to SE plus dynamic Gd-enhanced gradient-echo (GRE) pulse sequences. Forty-two patients with hepatic neoplasms were examined at 1.5 T field strength. In each patient, short and long repetition time/echo time (TR/TE) SE images were obtained, followed by pre- and post-Gd-DTPA (0.1 mmol/kg body wt), single-slice, breath-hold (13 s/scan) GRE images, which were serially acquired less than or equal to 12 min postinjection. The patterns of contrast enhancement of the various hepatic lesions were documented and analyzed. The time to peak Gd signal enhancement-to-noise ratio (SE/N), contrast-to-noise ratio (C/N), contrast (defined as the signal intensity ratio [SIR]), as well as the peak values of these quantities, were determined. The C/N and SIR values on the short and long TR/TE SE and pre-Gd GRE images for all hepatic neoplasms were also obtained. The discriminating abilities (hemangiomas vs. malignant neoplasms) of these quantities were analyzed statistically. In addition, the impact of lesion characterization on the SE versus the SE plus the Gd-enhanced GRE scans was assessed by means of a blinded reader study. Malignant hepatic neoplasms could be differentiated from hemangiomas by visual inspection of their enhancement patterns (p = 0.0009), by the time to peak C/N on Gd-enhanced images (p = 0.0002), and by the magnitude of such peak (p = 0.02). Combined SE + Gd-enhanced GRE scans afforded minor, though statistically significant (p less than 0.01), improvement of the accuracy in differentiating benign from malignant hepatic neoplasms. Late scans (12 min post-Gd) may be particularly useful in identifying hemangiomas that, unlike other neoplasms, have a significant high signal of their enhancing portions on such images.

Cervical carcinoma: MR imaging with an endorectal surface coil.

Ten consecutive patients with biopsy-proved invasive cervical carcinoma underwent magnetic resonance (MR) imaging with both a standard body coil and with an endorectal surface coil. The endorectal coil provided a markedly improved signal-to-noise ratio, enabling the use of small fields of view; thus, the images had significantly improved in-plane resolution. The images were assigned an MR imaging stage based on the clinical staging system of the International Federation of Gynecology and Obstetrics. Vaginal wall, vaginal fornix, parametrium, and pelvic side-wall invasion by tumor were all well demonstrated. When compared with body coil images, the endorectal coil images provided increased anatomic detail and demonstrated tissue planes between tumor and normal structures that were not seen on the body coil images. This preliminary investigation indicates that use of an endorectal surface coil is a promising technique to obtain high-resolution images of the female genital tract. This technique has the potential to improve the accuracy of staging for cervical carcinoma.

Integrated MR imaging and proton nuclear magnetic resonance spectroscopy in a family with an X-linked spastic paraparesis.

Seven members of a family with an X-linked spastic paraparesis syndrome were analyzed by MR imaging and stimulated echo, solvent-suppressed proton nuclear magnetic resonance spectroscopy. The MR scans of three symptomatic males and two asymptomatic females demonstrated abnormal signal in the supratentorial white matter. Each of these patients had a proton spectroscopic examination of a 2 X 2 X 2 cm voxel localized to the abnormal white matter of the centrum semiovale. The spectra demonstrated depression of N-acetyl aspartate/creatine, N-acetyl aspartate/choline, and creatine/choline ratios compared with normal control subjects. Additionally, these patients had abnormal elevations of amino acid resonances in the 2.1-3.0 ppm range. In a patient with symmetric white matter signal intensity abnormalities, an asymmetric spectroscopic study correlated with asymmetric symptoms. One asymptomatic family member with a normal MR study had abnormal metabolite ratio measurements. She was referred for further evaluation, since the proton spectrum suggested she may possess the affected gene. If the findings in this study are duplicated in other cases of hereditary dysmyelinating syndromes, we believe the integrated MR/proton nuclear magnetic resonance spectroscopy examination will be of benefit in evaluating and counseling families with familial dysmyelinating disorders.

Staging of ureteral transitional cell carcinoma by CT and MRI.

Intravenous urography and retrograde pyelography are the primary radiologic studies for detecting ureteral carcinoma but give limited information regarding stage of disease. Computed tomography (CT) and magnetic resonance imaging (MRI) delineate the extent of ureteral carcinomas with a high degree of accuracy by depicting the periureteral fat and presence or absence of lymphadenopathy. In selected cases, CT and MRI are valuable for assessing the presence or absence of tumor in a ureteral stump and for the differential diagnosis of ureteral obstruction. Five cases of ureteral carcinoma and 2 cases of stump carcinoma are presented with preoperative CT and/or MRI evaluation and staging.