XTC MRI: sensitivity improvement through parameter optimization.

Xenon polarization Transfer Contrast (XTC) MRI pulse sequences permit the gas exchange of hyperpolarized xenon-129 in the lung to be measured quantitatively. However, the pulse sequence parameter values employed in previously published work were determined empirically without considering the now-known gas exchange rates and the underlying lung physiology. By using a theoretical model for the consumption of magnetization during data acquisition, the noise intensity in the computed gas-phase depolarization maps was minimized as a function of the gas-phase depolarization rate. With such optimization the theoretical model predicted an up to threefold improvement in precision. Experiments in rabbits demonstrated that for typical imaging parameter values the optimized XTC pulse sequence yielded a median noise intensity of only about 3% in the depolarization maps. Consequently, the reliable detection of variations in the average alveolar wall thickness of as little as 300 nm can be expected. This improvement in the precision of the XTC MRI technique should lead to a substantial increase in its sensitivity for detecting pathological changes in lung function.

Evaluation of emphysema severity and progression in a rabbit model: comparison of hyperpolarized 3He and 129Xe diffusion MRI with lung morphometry.

The apparent diffusion coefficients (ADCs) of hyperpolarized (3)He and (129)Xe gases were measured in the lungs of rabbits with elastase-induced emphysema and correlated against the mean chord length from lung histology. In vivo measurements were performed at baseline and 2, 4, 6, and 8 wk after instillation of elastase (mild and moderate emphysema groups) or saline (control group). ADCs were determined from acquisitions that used two b values. To investigate the effect of b value on the results, b-value pairs of 0 and 1.6 s/cm(2) and 0 and 4.0 s/cm(2) were used for (3)He, and b-value pairs of 0 and 5.0 s/cm(2) and 0 and 10.0 s/cm(2) were used for (129)Xe. At 8 wk after instillation, the rabbits were euthanized, and the lungs were analyzed histologically and morphometrically. ADCs for the rabbits in the control group did not change significantly from baseline to week 8, whereas ADCs for the rabbits in the emphysema groups increased significantly (P < 0.05) for all gas and b-value combinations except (129)Xe with the b-value pair of 0 and 5.0 s/cm(2). The largest percent change in mean ADC from baseline to week 8 (15.3%) occurred with (3)He and the b-value pair of 0 and 1.6 s/cm(2) for rabbits in the moderate emphysema group. ADCs (all b values) were strongly correlated (r = 0.62-0.80, P < 0.001) with mean chord lengths from histology. These results further support the ability of diffusion-weighted MRI with hyperpolarized gases to detect regional and global structural changes of emphysema within the lung.

Cytological and biochemical studies of breast cyst fluid.

We determined the biochemical composition of fluid aspirated from 52 breast cysts and classified the cysts into types I and II on the basis of the potassium-to-sodium (K/Na) ratio in the fluid. In this study, we confirmed the presence of prostate-specific antigen (PSA) in some breast cyst fluids, regardless of whether cysts were type 1 or type 2, or benign or malignant. On immunohistochemical study, we found no direct correlation between the presence of PSA and progesterone receptors, which is at odds with the results of earlier reports. Current practice in cytologic study appears to favor the examination of bloody fluid. In this study, two samples found to contain malignant cells were cloudy or turbid. We therefore recommend that all cloudy or turbid cyst fluids should be subjected to cytologic examination. This study indicated that the potassium and sodium concentrations were not the same in multiple cysts in the same individuals. In addition, apocrine cells were observed in both type 1 and type 2 cysts. Therefore, breast cyst type cannot predict the natural history of cystic changes or indicate the likelihood of cancer. The finding of malignancy in two patients with type 2 cysts also supports this argument.

Hepatoid carcinoma of the ovary: characteristics of its immunoreactivity. A case report.

Alpha-fetoprotein producing tumors other than hepatoma and germ cell tumors have been widely reported, especially in carcinoma with hepatoid differentiation (hepatoid carcinoma). Hepatoid carcinoma has mostly been found in the stomach, but also occurs in many other organs. A rare case of hepatoid carcinoma of the ovary is presented. A 57-year-old Taiwanese woman was admitted because of lower abdominal pain. Magnetic resonance imaging showed a 10 cm right adnexal mass. She underwent a total hysterectomy and bilateral salpingo-oophorectomy with omentectomy. A right ovarian mass measuring 13 x 9 x 8 cm was found. Microscopic examination showed characteristic features for hepatoid carcinoma. Immunohistochemical staining was performed on the tumor using a panel of eight markers (AFP, p-CEA, CD10, Hep Par 1, thyroid transcription factor-1, CK7, CK19 and CK20). This study contradicts the theory that hepatoid carcinoma derives from the surface epithelium of the ovary. Hepatoid carcinoma of the ovary commonly contains a population of clear cells, which may lead to the misdiagnosis of yolk sac tumor or clear cell adenocarcinoma that may arise in many anatomic sites. Histologically, it is also difficult to distinguish hepatoid carcinoma from hepatoid yolk sac tumor. In such cases, demonstration of CD 10, Hep Par 1, membraneous patterns of p-CEA and CK7 would be invaluable for characterizing the tumor as hepatoid carcinoma. More studies are needed to confirm this observation.

Unique K-ras mutational pattern in pancreatic adenocarcinoma from Taiwanese patients.

To assess the prevalence and spectrum of K-ras mutations in Taiwanese patients with pancreatic adenocarcinoma, we analyzed 20 patients of ductal adenocarcinoma of the head of the pancreas undergoing pancreaticoduodenectomy. The study included K-ras mutations that were detected using DNA direct sequencing analysis of the polymerase chain reaction products and confirmed by reverse sequencing primers. The results showed that K-ras codon 12 mutation was detected in 90% of the cancer tissues (18/20). Moreover, the results from direct sequencing indicated that missense mutations were found to be a GGT to GTT in 94.5% of the cases (17/18) and a GGT to TTT in 5.5% of the cases (1/18). All cases with K-ras codon 12 mutations were found to be G to T transversion. However, no alterations were found at codons 13 and 61. From these findings, the high prevalence of K-ras codon 12 mutation in pancreatic adenocarcinoma and the predominant G to T transversion with the preferential substitution of glycine with valine might indicate an unusual sensitivity and specificity of this codon in genetic alterations for pancreatic carcinogenesis. The strikingly high mutational rate and the unique mutational spectrum of K-ras codon 12 in Taiwanese pancreatic adenocarcinoma can provide us with more information about the alternative diagnostic and therapeutic strategies in Taiwan.

Metastatic congenital adrenocortical carcinoma: a case report with tumor remission at 3 1/2 years.

We describe a case of metastasizing congenital adrenocortical carcinoma and a follow-up of 3 1/2 yr. Treatment with surgery and mitotane was associated with multiple complications. The patient was in remission at 3 1/2 yr. Because of the rarity of this condition, we discuss step-by-step problems encountered during management.

Case report: idiopathic giant cell granuloma of the hypophysis: an unusual cause of panhypopituitarism.

A 37-year-old man presented with headache and reduced libido. He suffered from panhypopituitarism, and the walls of the pituitary fossa were noted to be thickened, sclerotic, and irregular. Computed tomography scans showed an intrasellar and suprasellar, patchy enhancing tumor. From a biopsy taken at transsphenoidal surgery, a giant cell granuloma was diagnosed, for which there was no obvious cause. Inflammatory disease within the pituitary fossa should be suspected if a reaction is seen in the surrounding bone.

Creatine kinase isoenzymes in extracts of various human skeletal muscles.

We have attempted to "map" creatine kinase (CK; EC 2.7.3.2) anatomically by assaying biopsy specimens of skeletal muscles taken from different locations from 109 surgical patients. Substantial activities of CK-MM were present in every specimen; CK-MB was observed in about 44% of these, at approximately 1 to 6% of the total CK activity.

Creatine kinase and its isoenzymes in neoplastic disease.

The CK-BB isoenzyme is ubiquitous in neoplastic tissue, but with low activity. Accordingly, it might be a nonspecific and insensitive tumor marker. Evaluation of BB isoenzyme in serum might indicate the extent of diseases or the response to therapy. The presence of CK-MB in patients with cancers may cause confusion with AMI. Serial determinations of both CK and lactate dehydrogenase isoenzymes are of great help in differential diagnosis. The presence of mit-CK is a poor prognostic sign in patients with malignancy. The greatest clinical significance of CK-BB and macro-CK isoenzyme lies in their effect on various assays for CK-MB. Macro-CK types 1 and 2 are much more heat stable than are CK-MB and CK-BB, and so by heating samples for 20 min at 45 degrees C the presence of thermostable macro types can be demonstrated. Macro-CK type 2 has a much higher activation energy than macro-CK type 1. If macro-CK is present, determination of the activation energy easily differentiates between types 1 and 2. CK-Bi seems to be glycosylated protein, and it is thought that glycosylation may be a general way of enzyme inactivation. If inactivation inside the cell is postulated, it has to be shown that enzymes indeed pass into the cell compartments where glycosylating enzymes are located. Another possible mechanism is within the circulation. Whether malignant cells themselves produce Ck-Bi or if inactivation occurs in the blood is still unknown. In this connection, one finding is that in plasma of cancer patients, CK-Bi can be reactivated to CK-BB by mercaptoethanol to 95%, whereas in plasma of normal persons there is no reactivation of the much lower CK-Bi concentrations.