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.

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.

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.

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.

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.