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Biomedical subjects

L Kwock

Publications and source records attributed to L Kwock.

At least 37 records · Page 2Linked to original sources
PubMed1996

Postmortem MR imaging of lobar cerebral infarction with pathologic and in vivo correlation.

Postmortem magnetic resonance (MR) imaging features of different types of lobar cerebral infarction are correlated with the findings in gross and histologic specimens. The postmortem findings are also correlated with in vivo findings in similar cases selected from teaching files. In acute infarction, white matter vasogenic edema leads to high signal intensity on T2-weighted images and blurring of the gray-white matter junction. Petechial hemorrhage in the cortex results in inhomogeneous signal intensity on T2-weighted images. In laminar necrosis, the hyperintense cortex on T1-weighted images is due not to hemorrhage but possibly to necrosis and the presence of lipid-laden macrophages. In subacute infarction, cortical edema and necrosis may cause the gyral pattern of enhancement. Meningeal inflammation and early fibrosis are probably responsible for meningeal enhancement. In chronic infarction, gliosis and cystic malacia are responsible for the increased signal intensity of white matter on T2-weighted images. Knowledge of the pathologic features of cerebral infarction helps in understanding the MR imaging findings.

Acute Disease↗
PubMed1996

Proton MR spectroscopy of squamous cell carcinoma of the upper aerodigestive tract: in vitro characteristics.

PURPOSE: To determine the ability of in vitro high-field-strength proton MR spectroscopy to differentiate squamous cell carcinoma of the upper aerodigestive tract from uninvolved muscle. METHODS: Surgical specimens of squamous cell carcinoma arising from the upper aerodigestive tract (n = 18) and from muscle (n = 13) were examined in vitro using high-field (11 T) proton MR spectroscopy. The peak heights of choline and creatine were measured for tumor and muscle at echo times of 136 and 272. The choline/creatine (Cho/Cr) ratio was compared between tumor and normal tissue for each echo time. Student's t test was used to determine whether a significant difference existed between proton MR spectroscopic measurements of the Cho/Cr ratio for tumor and muscle. RESULTS: The mean Cho/Cr ratio was consistently higher in tumor than in muscle at all echo times; however, statistically significant differences between tumor and muscle were identified only at longer echo times (136 and 272). CONCLUSION: The Cho/Cr peak height ratio can be used to differentiate tumor from muscle in vitro (at 11 T).

Carcinoma, Squamous Cell↗
PubMed1995

MELAS syndrome: imaging and proton MR spectroscopic findings.

PURPOSE: To evaluate imaging findings in MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis, strokes) syndrome for the presence and location of infarctions and the presence of lactate. METHODS: Eight patients were studied with MR (n = 8) and CT (n = 2). One patient underwent single-photon emission CT with technetium 99m hexamethyl-propyleneamine oxime and one patient had conventional catheter angiography. One fixed brain was studied with MR imaging. Five patients underwent single volume proton MR spectroscopy. Imaging studies were evaluated for atrophy, edema, and infarctions. Proton MR spectroscopy was visually analyzed for presence or absence of lactate. RESULTS: One patient showed a cerebral infarction, and later a second distant infarction developed. One patient showed a transient area of cortical edema. Two patients had small nonspecific periventricular white matter abnormalities and one patient had diffuse white matter hyperintensities. Two patients had nonspecific MR abnormalities (probably age-related changes), and two had normal MR findings. None had basal ganglia involvement. Proton MR spectroscopy showed presence of lactate in one case with transient cortical edema; in two cases with nonspecific (probably age-related) brain findings; and in two patients with normal MR findings. CONCLUSIONS: Patients with MELAS have a variety of MR findings. The fact that proton MR spectroscopy showed lactate in all five cases studied, regardless of MR findings, indicates that proton MR spectroscopy may be more sensitive in the detection of MELAS-associated abnormalities than MR imaging.

Adolescent↗
PubMed1995

Proton MR spectroscopy in patients with neurofibromatosis type 1: evaluation of hamartomas and clinical correlation.

PURPOSE: To use proton MR spectroscopy in patients with neurofibromatosis type 1 to determine: (a) the spectroscopic characteristics of hamartomas and compare them with that of gliomas; (b) whether differences exist between patients with and without learning disabilities; and (c) spectroscopic patterns in normal-appearing brain (by MR imaging) in patients with and without focal lesions. METHODS: Seventeen proton MR spectroscopy volumes were obtained in 10 patients with neurofibromatosis type 1 (including hamartomas, N = 7; normal-appearing brain, N = 10). Seven patients had learning disorders, and 3 were mentally normal. Ten healthy volunteers and 10 patients with pathologically proved gliomas (all grades) were also examined. N-Acetyl aspartate/creatine, creatine/choline, and N-acetyl aspartate/choline ratios were calculated for all samples. RESULTS: (a) Hamartomas showed higher N-acetyl aspartate/creatine, creatine/choline, and N-acetyl aspartate/choline ratios than gliomas. Hamartomas showed N-acetyl aspartate/creatine, creatine/choline, and N-acetyl aspartate/choline ratios similar to those of healthy volunteers. (b) No significant differences in N-acetyl aspartate/creatine, creatine/choline, and N-acetyl aspartate/choline ratios were found in patients who had neurofibromatosis type 1 with and without learning disabilities. (c) N-acetyl aspartate/creatine, creatine/choline, and N-acetyl aspartate/choline ratios were similar for patients who had neurofibromatosis type 1 with and without focal hamartomas and in healthy volunteers. CONCLUSIONS: (a) Hamartomas have a proton MR spectroscopy pattern different from that of glioma and similar to that of normal brain. (b) As performed in this study, proton MR spectroscopy did not show significant differences in patients who had neurofibromatosis type 1 with and without learning disabilities. (c) Patients who have neurofibromatosis type 1 with and without hamartomas seem to have normal intervening brain by proton MR spectroscopy when compared with healthy volunteers.

Adolescent↗
PubMed1994

Magnetic resonance imaging and spectroscopy of small ring-enhancing lesions using a rat glioma model.

RATIONALE AND OBJECTIVES: We sought to demonstrate the usefulness of proton and fluorine magnetic resonance spectroscopy (MRS) techniques in characterizing small ring enhancing lesions produced by experimental malignant gliomas. METHODS: The growth characteristics of a rat glioma model (RT2) were studied using contrast-enhanced magnetic resonance imaging scans of the tumors and histologic correlates obtained at various times. Changes in tumor metabolite levels were monitored on a serial basis using water-suppressed proton spectroscopy. The existence of tumor hypoxia was established using 19F MRS in combination with a fluorinated nitroimidazole and subsequently confirmed by immunohistochemical staining of tumor sections. RESULTS: Ring-enhancing lesions are produced by RT2 rat brain gliomas approximately 7 days after intracerebral implantation. Beginning at day 5, marked deviations in brain metabolite levels are observed on proton MR spectra. However, while the signal from the fluorinated nitroimidazole is first detected by 19F MRS at day 7, immunohistochemical staining of tissue sections reveals bound drug as early as day 5, when the first histologic signs of necrosis become apparent. CONCLUSIONS: Magnetic resonance imaging of RT2 rat brain glioma exhibits ring-enhancing characteristics similar to those observed in clinical studies. The appearance of the ring enhancement corresponds with the development of central necrosis and could serve as an indicator for rapid growth. Proton and fluorine MRS may be useful in confirming that a small ring-enhancing lesion represents an active tumor process early in its development.

Animals↗
PubMed1992

Evaluation of a fluorinated 2-nitroimidazole binding to hypoxic cells in tumor-bearing rats by 19F magnetic resonance spectroscopy and immunohistochemistry.

We have examined a hexafluorinated 2-nitroimidazole, CCI-103F, as a probe for hypoxic tumor cells by in vivo 19F magnetic resonance spectroscopy (MRS). Following initial intraperitoneal injections of the drug in tumor-bearing (Dunning R3327-AT1-Matlylu) rats, 19F spectra were obtained on an Otsuka 2.0T Vivospec spectrometer using a 1.5-cm surface coil. Signal at 1- and 2-h time points indicated initial biodistribution of drug in the tumor. At 4 and 8 h, a progressive increase in signal intensity was observed, indicating retention of drug within the tumor. Tumor signal remained detectable in 4 of 10 rats at 24 h, indicating possible nitroreductive bioactivation by hypoxic cells. Immunohistochemistry of these tumors revealed a staining pattern consistent with labeling of hypoxic cells. No detectable 19F signal was found at 24 h for the other rats, indicating complete washout of unbound drug. Immunohistochemical assessment of these tumors revealed some staining for bound drug at the periphery of necrotic zones. 31P-MRS of the tumors showed good correlation with the presence or absence of hypoxia as evaluated by 19F-MRS, T1- and T2-weighted images, and immunohistochemistry. These results provide the groundwork for further studies using this misonidazole analog for noninvasive identification of hypoxic tumor cells in vivo by MRS.

Adenocarcinoma↗
PubMed1991

Parameter optimization and calibration of 19F magnetic resonance imaging at 1.5 Tesla.

Fluorine-19 magnetic resonance imaging is limited by the fact that acquisition times are long and that high concentrations must be used in order to obtain good signal to noise. A significant improvement in signal to noise ratio may be brought about by the addition of Gd-DTPA, a paramagnetic agent which shortens T1. Images of phantoms containing trifluoroacetic acid (TFA) doped with Gd-DTPA were obtained using a standard spin echo sequence in a 1.5 T field. Interpulse times (TR and TE) and Gd-DTPA concentrations were optimized to yield maximum signal to noise ratios. The use of fast-field-echo scans to image fluorine is also demonstrated. Signal averaging successive FFE scans yields good signal to noise and resolution and may find clinical applicability in imaging areas subject to motion.

Calibration↗
PubMed1991

Stereotactic intratumoral photodynamic therapy for recurrent malignant brain tumors.

Photodynamic therapy (PDT) using purified hematoporphyrin derivative and stereotactic intratumorally implanted optical laser fiber(s) was used to treat patients with recurrent malignant gliomas and metastatic melanoma of the brain. Tumor response to PDT was evaluated by recording changes in the volume and pattern of tumor enhancement between computed tomographic and magnetic resonance imaging scans done before and after PDT, metabolic changes in tumor tissue by 31P magnetic resonance spectroscopy, and patient outcome. Toxicity of PDT to brain was evaluated on the basis of changes in the patients' neurological examinations and correlated with changes in brain adjacent to tumor seen on postoperative imaging studies. Dramatic tumor responses to PDT were seen in all gliomas, but no response of tumor to treatment was seen with melanoma. Transient signs and symptoms of increased peritumoral cerebral edema caused by PDT were seen in all patients. Two patients suffered permanent neurological sequelae, monocular blindness and a partial visual field defect, as a result of treatment. Two patients with recurrent anaplastic astrocytomas remain in remission at 45 and 35 weeks after PDT. We conclude that intratumoral photoradiation therapy of hematoporphyrin derivative-photosensitized malignant gliomas effectively produces necrosis of the solid component of malignant gliomas; however, intratumoral photoradiation may not reach the portion of tumor that invades normal brain.

Adult↗
PubMed1989

In vitro NMR evaluation of human thyroid lesions.

In vitro analysis of spin-lattice relaxation times (T1), water self-diffusion coefficients (DH2O), and proton NMR spectroscopy were performed in a study of 88 patients with thyroid lesions in order to determine the usefulness of these parameters in the differentiation of benign and malignant tissues. Thyroid tissue sample proton NMR spectral patterns were examined at 360 MHz. Proton NMR spectra were different for normal thyroid tissues, benign, and cancerous lesions. Significantly prolonged T1 (0.5T) and decreased DH2O were found in cancerous thyroid lesions relative to normal thyroid tissues. Considerable overlap was found, however, in comparing T1 and DH2O values for benign and malignant thyroid lesions. This study suggests that proton NMR spectroscopy may be more useful than T1 and DH2O in differentiating benign and malignant thyroid lesions.

Adenoma↗
PubMed1987

Fluorine-19 NMR studies of tumor-bearing rats treated with difluoromethylornithine.

Copenhagen rats with implanted metastatic prostate carcinomas have been treated with the drug alpha-difluoromethylornithine (DFMO), an inhibitor of the enzyme ornithine decarboxylase. In vivo and in vitro 19F NMR observations were then carried out on a variety of organs and tissues. The distribution of the drug strongly favored tumor over surrounding muscle. DFMO, which gives a spectrum similar to that of the pH indicator difluoromethylalanine, has potential for determination of in vivo pH. However, in contrast to the alanine analog, DFMO exhibits a considerably smaller shift dependence in response to pH changes.

Adenocarcinoma↗
PubMed1987

Reduced oxygen tension induces pulmonary endothelium to release a pulmonary smooth muscle cell mitogen(s).

Bovine pulmonary endothelial cells grown in vitro were shown to release a factor that was mitogenic for pulmonary smooth muscle cells during exposure to a reduced oxygen tension atmosphere. The addition of hypoxic endothelium-derived medium resulted in a 60% increase in smooth muscle cell number after 24 h of exposure. Addition of medium from pulmonary endothelium exposed to normoxic conditions or medium derived from either hypoxic or normoxic aortic endothelium did not result in significant increases in smooth muscle cell number. Physicochemical characterization of the hypoxic pulmonary endothelial cell-derived factor(s) showed that it was resistant to heat and reducing agent treatment and stable between pH 3 and 10. The mitogenic activity decreased by 71% at pH 2 and by 68% after treatment with trypsin. The activity adhered to DEAE Sephadex. Gel filtration chromatography of the hypoxic-conditioned medium demonstrated 2 major peaks of smooth muscle cell growth factor activity corresponding to molecular weights between 6,000 and 14,000 and 20,000 and 65,000 daltons, respectively. These data suggest that this pulmonary endothelial cell-derived smooth muscle cell peptide mitogen(s) may be involved in the smooth muscle cell proliferative response seen with chronic alveolar hypoxia.

Animals↗
PubMed1987

The effects of ionizing radiation on the pulmonary vasculature of intact rats and isolated pulmonary endothelium.

We studied the effects of ionizing radiation on the morphology of the pulmonary circulation using an in vivo rat model and an in vitro pulmonary artery endothelial cell model. Gamma radiation was given as either an acute (30 Gy) or fractionated (5 X 6 Gy) dose to one hemithorax of rats. An acute 30-Gy dose delivered resulted in a 70% decrease in pulmonary arterial perfusion, using technetium-99m microaggregated albumin (99mTc-MAA), in the irradiated lung by 2-3 weeks after irradiation. Pulmonary microradiographs, using a barium sulfate perfusion method, obtained 2-3 weeks after irradiation demonstrated widespread loss of capillary filling and segmentation of the vessels. Histologic examination demonstrated intact capillaries, suggesting that the alterations in pulmonary perfusion were at the precapillary level. Similar abnormalities in lung perfusion and morphology were found after delivery of fractionated doses of radiation, but the onset of the changes was delayed, occurring 4-6 weeks postirradiation. Using cultured pulmonary endothelial cell monolayers, cell sloughing and retraction from the surface substrate were observed within 24 h after in vitro delivery of 30 Gy. Similar findings occurred in monolayers given fractionated doses (5 X 6 Gy) of radiation 2-3 days after the final dose. The in vivo animal and in vitro endothelial cell models offer a useful means of examining the morphologic alterations involved in radiation lung vascular damage.

Animals↗
PubMed1986

Reversible alterations in cultured pulmonary artery endothelial cell monolayer morphology and albumin permeability induced by ionizing radiation.

The effects of ionizing irradiation (0, 600, 1,500, or 3,000 rads) on the permeability of pulmonary endothelial monolayers to albumin were studied. Pulmonary endothelial cells were grown to confluence on gelatin-coated polycarbonate filters, placed in serum-free medium, and exposed to a 60Co source. The monolayers were placed in modified flux chambers 24 hours after irradiation; 125I-albumin was added to the upper well, and both the upper and lower wells were serially sampled over 4 hours. The amount of albumin transferred from the upper well/hour over the period of steady-state clearance (90-240 min after addition of 125I-albumin) was 2.8 +/- 0.2% in control monolayers and was increased in monolayers exposed to 1,500 or 3,000 rads (increase of 63 +/- 10% and 61 +/- 10%, respectively, P less than 0.01). No increase was found in monolayers exposed to 600 rads. The increases in endothelial albumin transfer rates were associated with morphologic evidence of monolayer disruption and endothelial injury which paralleled the changes in albumin permeability. Dose-dependent alterations in endothelial actin filament organization were also found. Incubation of the monolayers exposed to 3,000 rads with medium supplemented with 10% fetal calf serum for 24 hours resulted in normalization of albumin permeability, improvement in morphologic appearance of the monolayers, and reorganization of the actin filament structure. These studies demonstrate that ionizing radiation is an active principle in the reversible disorganization of cultured pulmonary endothelial cell monolayers without the need of other cell types or serum components.

Albumins↗
PubMed1986

The effects of ionizing radiation on the pulmonary endothelial cell uptake of alpha-aminoisobutyric acid and synthesis of prostacyclin.

The effects of gamma irradiation (150-3000 rad) on prostacyclin synthesis (PGI2) and Na+-dependent amino acid uptake (alpha-aminoisobutyric acid, AIB) were assessed in vitro in bovine pulmonary artery endothelial cells grown in plastic culture dishes. A dose-dependent increase in both PGI2 synthesis and AIB was found 24 h after irradiation at exposure levels greater than 600 rad. The increase in PGI2 synthesis [297% of sham-irradiated values at 3000 rad, P less than 0.01] was due to an increase in release of arachidonic acid from plasma membrane stores as well as stimulation of cyclooxygenase and/or prostacyclin synthetase enzymes. The increase in AIB uptake (75% increase at 3000 rad compared to sham-exposure values) correlated with the increased synthesis of PGI2 (r = 0.94). There was also a dose-dependent increase in the number of cells that became detached from the culture dishes during the 24-h period after irradiation. The changes in PGI2 synthesis and AIB uptake induced by gamma irradiation differed if the endothelial cells were grown on cover slips, indicating that the endothelial response to irradiation may be dependent on the interaction between the endothelial cell and its extracellular basement membrane matrix.

Aminoisobutyric Acids↗
PubMed1986

Actin filament organization of the Dunning R3327 rat prostatic adenocarcinoma system: correlation with metastatic potential.

Recently, Volk, Geiger, and Raz (Cancer Res., 44: 811-824, 1984) addressed the question of whether variations in actin organization in clones of the murine K-1735 melanoma tumor correlated with their metastatic capability. Using immunofluorescence techniques, they found that clones which had a more ordered actin network were less metastatic, whereas clones having a diffuse actin staining pattern were more metastatic. Similarly, we have found that in the Dunning rat R3327 prostatic adenocarcinoma tumor system, the non-metastatic (less than 0.1%) H-prostatic tumor cell line has a prominent network of actin filament bundles, whereas the highly metastatic (greater than 90%) MatLyLu cell line has a diffuse actin staining pattern. In the low-metastatic (less than 10%) AT1 cell line an intermediate actin organization between H and MatLyLu was observed. Analysis of cell extracts from H- and MatLyLu-cells revealed differences in the level of activity of cellular proteins which affect actin filament assembly and structure in a manner similar to that of the cytochalasins, fungal metabolites which bind with high affinity to the fast-growing end of actin filaments. Extracts of MatLyLu were significantly more effective than those of H-cells in decreasing the extent of actin filament network formation and in inhibiting the rate of filament assembly by blocking monomer addition onto the fast-growing end. Measurements of spin-lattice nuclear magnetic resonance water proton relaxation times (T1) were made in surgically removed tumor tissue from four sublines (H, AT1, MatLyLu, and MatLu) of the Dunning R3327 tumor system. The highly metastatic cell lines had significantly longer water proton T1 relaxation times than did the lines with low metastatic potential. These differences in T1 may reflect the observed alterations in organization of actin filaments within these various sublines of the Dunning R3327 prostatic adenocarcinoma tumor system.

Actin Cytoskeleton↗