Temporomandibular joint and 3.0 T pseudodynamic magnetic resonance imaging. Part 1: evaluation of condylar and disc dysfunction.

OBJECTIVES: This study describes an improved method for examining and diagnosing temporomandibular joint (TMJ) dynamics by 3.0 T pseudodynamic MRI. METHODS: Clinical observation and conventional static MRI of volunteers (one without and eight with TMJ arthrosis) were followed by 3.0 T pseudodynamic MRI in positions ranging from the mouth closed to mouth fully opened. Condylar head (Cd), articular disc anterior border (Da) and articular disc posterior border (Dp) were digitized on sagittal images to determine trajectory and velocity patterns. RESULTS: Patients were divided into three groups based on the presence or absence of dysfunction: Group 1, no dysfunction on the right or left side of the TMJ; Group 2, dysfunction on the right or left side of the TMJ; and Group 3, dysfunction on both the right and left sides of the TMJs. In 75% of patients (12 of 16 joints), pseudodynamic TMJ analysis was useful for determining a functional abnormality. Using a points system based on three trajectory and seven velocity patterns, discs with adhesion and perforation had significantly fewer points than discs with anterior displacement (with and without reduction) and discs with no abnormality (P = 0.019 < 0.05). CONCLUSIONS: Trajectory and velocity patterns based on 3.0 T pseudodynamic MRI identified the affected side and determined the extent of morbidity in the Cd as well as the Da and Dp. The typical abnormal movement pattern of discs with anterior displacement (with and without reduction) and pathological structural changes of the articular disc (such as adhesion and perforation) could be identified.

Temporomandibular joint and 3.0 T pseudodynamic magnetic resonance imaging. Part 2: evaluation of articular disc obscurity.

OBJECTIVES: This study examined the relationship between temporomandibular joint (TMJ) dysfunctions and obscurity grades of interpreted anterior and posterior borders of the articular disc (Da and Dp, respectively) by 3.0 T pseudodynamic MRI. METHODS: Da and Dp were classified into seven obscurity grades, and the Dp contour was classified into three types. The grades, types and TMJ function were compared by 3.0 T pseudodynamic MRI. RESULTS: Unobscured Da images at condylar positions posterior to the articular eminence were associated with normal TMJ function (P = 0.046 < 0.05). Unobscured Dp images at condylar positions anterior to the articular eminence were associated with normal TMJ function (P = 0.033 < 0.05). In addition, unobscured Dp images following flap insertion were associated with normal TMJ function (P = 0.043 < 0.05). There was no statistical relationship between Dp contour types and TMJ movement, but any change observed in the Dp contour during mouth opening was associated with abnormal TMJ function (P = 0.040 < 0.05). CONCLUSIONS: Grading of Da and Dp obscurity based on how well the areas were defined in the images, identifying the condylar positions in relation to the glenoid fossa and articular eminences, and observing the changes in Dp contour types were useful for diagnosing TMJ abnormalities.

Diffusion-weighted magnetic resonance imaging of endometrial cancer: differentiation from benign endometrial lesions and preoperative assessment of myometrial invasion.

BACKGROUND: Uterine endometrial cancer is the most common gynecologic malignancy, and benign endometrial hyperplasia or polyps should be differentiated from endometrial cancer. In evaluating endometrial cancer on magnetic resonance imaging (MRI), the assessment of the depth of myometrial invasion is important because it closely correlates with the patient's prognosis. PURPOSE: To verify the feasibility of diffusion-weighted magnetic resonance imaging (DWI) to distinguish benign and malignant endometrial lesions, and to evaluate myometrial invasion of endometrial cancer. MATERIAL AND METHODS: Sixty-seven endometrial lesions including 45 cancers and 22 benign lesions (hyperplasia and polyps) were evaluated by DWI with apparent diffusion coefficient (ADC) measurement. The staging accuracies of DWI and gadolinium-enhanced T1-weighted images in the assessment of myometrial invasion were evaluated in 33 patients with endometrial cancer. RESULTS: The ADC values (x10(-3) mm(2)/s) in cancer and benign lesions were 0.84+/-0.19 and 1.58+/-0.36, respectively (P<0.01). The staging accuracy (superficial or deep myometrial invasion) was 94% for DWI and 88% for gadolinium-enhanced T1-weighted images. Coexisting adenomyosis and infiltrative myometrial invasion caused staging errors on gadolinium-enhanced T1-weighted images, whereas DWI could demonstrate the tumor extent correctly. CONCLUSION: DWI provides helpful information in evaluating benign and malignant endometrial lesions.

Diffusion-weighted magnetic resonance imaging of urinary epithelial cancer with upper urinary tract obstruction: preliminary results.

BACKGROUND: Various malignant tumors of the body show high signal intensity on diffusion-weighted magnetic resonance imaging (DWI). In the genitourinary region, DWI is expected to have a role in detecting urinary epithelial cancer noninvasively. PURPOSE: To demonstrate the feasibility of DWI for the diagnosis of urinary epithelial cancer with upper urinary tract obstruction. MATERIAL AND METHODS: Twenty upper urinary tract cancers in 16 patients were evaluated by high-b-value DWI (b=800 s/mm(2)). The signal intensity was visually evaluated, and the apparent diffusion coefficients (ADCs) were measured. RESULTS: All urinary epithelial cancers showed high signal intensity on DWI. The ADC in cancerous lesions was 1.31+/-0.27 x 10(-3) mm(2)/s, which was significantly lower than that of the lumens of the ureter or renal pelvis (3.32+/-0.44 x 10(-3) mm(2)/s; P<0.001). Maximum intensity projection images of DWI in combination with static-fluid MR urography provided three-dimensional entire urinary tract imaging with the extension of tumors. CONCLUSION: DWI is useful in the tumor detection and in evaluating the tumor extension of urinary epithelial cancer in patients with upper urinary tract obstruction.

High-b-value diffusion-weighted magnetic resonance imaging of pancreatic cancer and mass-forming chronic pancreatitis: preliminary results.

BACKGROUND: Mass-forming chronic pancreatitis may mimic a pancreatic cancer on dynamic computed tomography (CT) and magnetic resonance (MR) imaging, and preoperative differential diagnosis is often difficult. Recently, the usefulness of diffusion-weighted MR imaging (DWI) in the diagnosis of pancreatic cancer has been reported in several studies. PURPOSE: To determine whether high-b-value DWI can distinguish pancreatic cancer from benign mass-forming chronic pancreatitis. MATERIAL AND METHODS: Twenty pancreatic cancers and four cases of mass-forming chronic pancreatitis were evaluated by high-b-value DWI (b=800 s/mm(2)). The signal intensity on DWI was visually evaluated, and the isotropic apparent diffusion coefficients (ADCs) were measured. RESULTS: All twenty pancreatic cancers showed high signal intensity (18 showed very high, two showed slightly high) on DWI. None of the mass-forming chronic pancreatitis cases showed very high intensity (three showed iso to low, one showed slightly high) on DWI. The ADCs in the pancreatic cancer and mass-forming chronic pancreatitis were 1.38 +/- 0.32 x 10(-3) mm(2)/s and 1.00 +/- 0.18 x 10(-3) mm(2)/s, respectively (P < 0.05). CONCLUSION: On high-b-value DWI, most pancreatic cancers showed very high signal intensity, and may hence be distinguished from benign mass-forming chronic pancreatitis based on our preliminary results.

Case report: A case of polypoid endometriosis: MR pathological correlation.

We report a case of polypoid endometriosis and correlate the MRI findings with the pathological findings. The polypoid endometriosis appeared as multiple polypoid masses protruding into the adjacent pelvic organs, including the uterus and rectum. The masses were found to show hyperintensity on T(2) weighted images, which was similar to the signal intensity of the uterine endometrium, reflecting the presence of abundant endometrial-type glands. The masses were also surrounded by hypointense rim-like structures on T(2) weighted images. These structures were confirmed by pathology to correspond with fibrous tissues arising from endometriosis. These features, together with an intense enhancement similar to the adjacent uterus, may be a diagnostic clue to this rare entity.

Hanging protocol and viewers for a dental full picture [corrected] archiving and communication system (PACS) [corrected].

OBJECTIVES: Study objectives were: to develop a hanging protocol for displaying digital transmission radiographic images of oral and maxillofacial regions using a dental DICOM (digital imaging and communication in medicine) viewer and a dental Web viewer; and to give information on a system that allows patients and health professionals to share image information. METHODS: For the hanging protocol, alphanumeric tags were defined and used in a DICOM modality worklist. These tags consisted of layout information to display images on monitors by the type of projection method and assignment information to display images of template for intraoral full-mouth survey that were numbered and slotted according to tooth position. Tooth code and algorithm for assignment of images for intraoral full-mouth survey were determined. Expanded correspondence for viewers was used for modalities without tags. Images could be edited by quality control system. An electronic medical record (EMR) system, a radiological information system (RIS) and a picture archiving and communication system (PACS) with servers, terminals and viewers were set up in a patient-centred hospital environment. RESULTS: Using the hanging protocol, the viewers displayed digital transmission radiographic images automatically on display areas on one or multiple monitors showing intraoral, panoramic and extraoral views produced during various examinations. The images were also displayed using the coupling function of EMR and RIS. Users can compare the images taken at various times more efficiently. CONCLUSION: The new system using a dental DICOM viewer and a dental Web viewer is the most advanced for examining oral and maxillofacial regions compared with medical viewers. Our local but clinically operational hanging protocol should be a good model for DICOM Working Group 22.

Licensing regulators Geminin and Cdt1 identify progenitor cells of the mouse CNS in a specific phase of the cell cycle.

Nervous system formation integrates control of cellular proliferation and differentiation and is mediated by multipotent neural progenitor cells that become progressively restricted in their developmental potential before they give rise to differentiated neurons and glial cells. Evidence from different experimental systems suggests that Geminin is a candidate molecule linking proliferation and differentiation during nervous system development. We show here that Geminin and its binding partner Cdt1 are expressed abundantly by neural progenitor cells during early mouse neurogenesis. Their expression levels decline at late developmental stages and become undetectable upon differentiation. Geminin and Cdt1 expressing cells also express Sox2 while no overlap is detected with cells expressing markers of a differentiated neuronal phenotype. A fraction of radial glial cells expressing RC2 and Pax6 are also immunoreactive for Geminin and Cdt1. The majority of the Geminin and Cdt1 expressing cell populations appears to be distinct from fate-restricted precursor cells expressing Mash1 or Neurogenin2. Bromo-deoxy-uridine (BrdU) incorporation experiments reveal a cell cycle specific expression in neural progenitor cells, with Geminin being present from S to M phase, while Cdt1 expression characterizes progenitor cells in G1 phase. Furthermore, in vitro differentiation of adult neurosphere cultures shows downregulation of Geminin/Cdt1 in the differentiated state, in line with our data showing that Geminin is present in neural progenitor cells of the CNS during mouse embryogenesis and adulthood and becomes downregulated upon cell fate specification and differentiation. This suggests a role for Geminin in the formation and maintenance of the neural progenitor cells.

[Quality control (QC) of CT on rail system (FOCAL Unit) with a micro-multi leaf collimator (mMLC) using new GafChromic film for stereotactic radiotherapy].

PURPOSE: Recent years, CT on rail system was reported to be useful as a tool for image-guided radiotherapy (IGRT). This system was clinically developed with the aim of stereotactic irradiation (STI) for brain, lung, liver, prostate and other sites. Quality assurance and quality control (QC) is an important issue in CT on rail system to assure geometric accuracies. The purpose of this study is to estimate the geometric accuracies of our CT on rail system using a detachable micro-multi leaf collimator (mMLC) with new type radiochromic films. Carrying out our original QC program, translational errors, setup reproducibility, beam misalignment and beam characteristics were evaluated. METHODS AND MATERIALS: We have studied with CT on rail system (FOCAL unit, Toshiba Medical systems, Tokyo, Japan) and mMLC unit (Accuknife, Direx Inc., Tokyo, Japan). We have developed original alignment phantom and small steel markers (2 mm phi) were implanted on its surface at certain intervals. Firstly, we have evaluated the accuracy of self-moving CT gantry and CT resolutions for cranio-caudal directions by changing slice thickness. And then using the phantom, we have measured the accuracy and reproducibility of geometric isocenter of the linac side and the CT gantry side by scanning the phantom. We have also measured the geometric changes of the common treatment couch by weight-loaded test (up to 135 kgw). To estimate dosimetric and geometric accuracies with the mMLC unit, the misalignment of the beam axes (gantry, collimator and couch rotation axis), mMLC leaf positions, and dose distributions for the verification plan were measured with new type GafChromic films (GafChromic-RTQA, ISP Inc., USA) and cylindrical phantom. The dose characteristics of the GafChromic film were also evaluated. RESULTS: The reproducibility of the self-moving CT gantry have a good agreement within 1 mm. Weight-load test have shown a good reliability within 2 mm at the common treatment couch. The translational precision of the common treatment couch was 0.0 +/- 0.1 mm at linac side and -0.2 +/- 0.5 mm at CT gantry side. The misalignments of beam axes have been kept within 0.4 mm at maximum. Gap test have shown the accuracies of the mMLC leaf positions, which is needed to keep within 1 mm by a routine calibration. CONCLUSIONS: To practice quality control program for the FOCAL unit and the mMLC unit is essential for a regular interval to reduce systematic errors. New type radiochromic film would be useful for a verification tool as alternative to conventional film.

Expression of the licensing factors, Cdt1 and Geminin, in human colon cancer.

Licensing of chromatin for replication is an evolu-tionarily conserved step in the control of cell division and genomic integrity. Proteins that participate in licensing have been recently documented to denote the proliferative state of cells and they have been proposed as diagnostic and prognostic markers in human cancer. Cdt1 was recently discovered as an important licensing factor, that is inhibited by Geminin. In the present study we analyzed Cdt1 and Geminin expression in human colon cancer. We showed that Cdt1 protein is highly expressed in human neoplastic lesions of the colon while its cell-cycle phase-specific expression profile appears preserved during human carcinogenesis. Similarly, Geminin, Cdt1's inhibitor, is also overexpressed in colon carcinomas and its expression correlates with significant clinicopathological parameters of the disease. Moreover, both Cdt1 and Geminin expression are severely downregulated upon differentiation of Caco-2 cells, an in vitro model of intestinal epithelial differentiation.

DNA replication licensing.

The DNA replication licensing system ensures that chromosomal DNA is replicated precisely once before cell division occurs. A DNA helicase must be loaded on origin DNA for replication to initiate. Considerable evidence suggests that the MCM complex acts as a replicative helicase in eukaryotes. When the MCM complex is loaded on the chromatin, the replication origin is formally defined as being licensed for replication. Licensing takes place several hours before origins are activated to undergo replication in S-phase. Genetic and biochemical studies show that the licensing process is well conserved in eukaryotes. Cyclin Dependent Kinases (CDKs), the master regulators of the cell cycle, coordinate the initiation of the two key cell cycle events, replication of DNA and its segregation at mitosis. Eukaryotes have developed complex regulatory mechanisms to ensure that origin licensing is coordinated with these events so that genome integrity is preserved during successive cell divisions.

Imaging findings of urachal mucinous cystadenocarcinoma associated with pseudomyxoma peritonei.

Pseudomyxoma peritonei is an uncommon neoplastic condition in which gelatinous fluid-like materials are observed in the peritoneal cavity caused by the dissemination of mucinous adenocarcinoma. Although ruptured appendiceal mucocele is the most common cause, tumors arising from other organs may also cause pseudomyxoma peritonei. We report the imaging findings of an extremely rare case of urachal mucinous adenocarcinoma associated with pseudomyxoma peritonei on computed tomography and magnetic resonance imaging with histopathologic correlation.

A novel nuclear protein, Twa1, and Muskelin comprise a complex with RanBPM.

A truncated human RanBPM has been isolated as a protein binding to Ran, Ras-like nuclear small GTPase. Full-sized human RanBPM cDNA which was recently isolated, was found to encode a protein of 90 kDa which comprises a large protein complex. Consistent with this finding, several proteins were found to be co-precipitated with RanBPM by immunoprecipitation analysis. Accordingly, in the present study, we screened the human cDNA library by the two-hybrid method using RanBPM cDNA as bait. One novel protein designated as Twa1 (Two hybrid associated protein No. 1 with RanBPM), and two known proteins, a human homologue (hMuskelin) of mouse Muskelin and HSMpp8 were isolated repeatedly. Twa1 was well conserved through evolution and was localized within the nucleus. Interestingly, in addition to Muskelin and RanBPM, Twa1 was found to possess the LisH-CTLH motif which is detected in proteins involved in microtubule dynamics, cell migration, nucleokinesis and chromosome segregation. These functions overlap with functions suggested for the RanGTPase cycle. Immunoprecipitation and gel-filtration analyses indicated that both Twa1 and hMuskelin did indeed comprise a protein complex with RanBPM. Taken together with the fact that RanBPM interacts with Ran, our present findings suggested that there is an as yet uncovered function of the RanGTPase cycle.

A characteristic feature of acute haematomas in the brain on echo-planar diffusion-weighted imaging.

Diffusion-weighted MRI (DWI) is used in the diagnosis of acute ischaemic disease of the brain, but it is not clear whether or not it can be used to differentiate an acute haematoma from an infarct. Our purpose was to identify any characteristic feature of acute haematomas which can be recognised on DWI and to evaluate the usefulness of DWI in acute cerebral stroke. We examined nine patients with acute haemorrhage using CT and MRI including DWI. We measured the volume and apparent diffusion coefficient (ADC) of the haematomas. All showed heterogeneous signal on DWI, and the centre of the large (>20 ml) haematomas especially a mixed pattern with high and low signal. The characteristic feature of acute haematomas was a peripheral low-signal region, found in all subjects regardless of the size of the haematoma; acute infarcts did not show this. This low-signal rim on DWI may be useful for differentiating an acute haematoma from an infarct.

The human licensing factor for DNA replication Cdt1 accumulates in G1 and is destabilized after initiation of S-phase.

S-phase onset is controlled, so that it occurs only once every cell cycle. DNA is licensed for replication after mitosis in G(1), and passage through S-phase removes the license to replicate. In fission yeast, Cdc6/18 and Cdt1, two factors required for licensing, are central to ensuring that replication occurs once per cell cycle. We show that the human Cdt1 homologue (hCdt1), a nuclear protein, is present only during G(1). After S-phase onset, hCdt1 levels decrease, and it is hardly detected in cells in early S-phase or G(2). hCdt1 can associate with the DNA replication inhibitor Geminin, however these two proteins are mostly expressed at different cell cycle stages. hCdt1 mRNA, in contrast to hCdt1 protein, is expressed in S-phase-arrested cells, and its levels do not change dramatically during a cell cycle, suggesting that proteolytic rather than transcriptional controls ensure the timely accumulation of hCdt1. Consistent with this view, proteasome inhibitors stabilize hCdt1 in S-phase. In contrast, hCdc6/18 levels are constant through most of the cell cycle and are only low for a brief period at the end of mitosis. These results suggest that the presence of active hCdt1 may be crucial for determining when licensing is legitimate in human cells.

Multivariate analysis of regional metabolic differences in normal ageing on localised quantitative proton MR spectroscopy.

We performed multivariate analysis of regional differences and normal age-related changes in metabolites in the lentiform nucleus and frontal lobe, as measured by proton MRS. The cerebrospinal fluid (CSF) in the measurement area was estimated and the metabolite concentration adjusted. The concentration of N-acetylaspartate (NAA) in the lentiform nucleus decreased with ageing (F = 4.11, P < 0.01), but that in the frontal lobe did not change (F = 0.93, P = 0.45). This is in marked contrast with pathological dementia, such as Alzheimer's disease. In this multivariate analysis, the normal change in metabolism with ageing differed depending on the cerebral region, suggesting that metabolite concentrations, especially that of NAA may be useful metabolic indices for discriminate normal ageing from pathological dementia.

Regional magnetic resonance spectroscopy of the brain in autistic individuals.

We studied the variations in the concentration of metabolites with brain region and age in autistic individuals and normal controls using multiple analysis of covariance. We examined 55 autistic individuals (2-21 years old, 47 male and eight female) and 51 normal children (3 months-15 years old, 26 boys and 25 girls). Single volumes of interest were placed in the frontal, parietal and temporal region on both sides, the brain stem and cingulate gyrus. The concentration of each metabolite was quantified by the water reference method. The concentration of N-acetylaspartate in the temporal regions (Brodmann's areas 41 and 42) in the autistic individuals were significantly lower than those in the controls (P < 0.05), but concentrations in other regions were not significantly different between the autistic individuals and controls. This suggests low density or dysfunction of neurones in Brodmann's areas 41 and 42 in autistic individual, which might be related to the disturbances of the sensory speech centre (Wernicke's area) in autism.

Full-sized RanBPM cDNA encodes a protein possessing a long stretch of proline and glutamine within the N-terminal region, comprising a large protein complex.

Previously isolated RanBPM, a Ran-binding protein in the microtubule-organizing center, which had been thought to play a role in Ran-stimulated microtubule assembly, turned out to be a truncated protein. To clarify the function of RanBPM, we cloned the full-sized RanBPM cDNA that encodes a 90 kDa protein, compared to the previously isolated cDNA that encoded a 55 kDa protein. The newly cloned 5' coding region contains a great number of cytidine and guanidine nucleotides, like the CpG island. Thus, full-sized RanBPM cDNA encodes a long stretch of proline and glutamine residues in the N-terminal region. It comprises a protein complex of more than 670 kDa. Ran was detected in this complex when RanBPM and Ran were both ectopically expressed. New antibodies to RanBPM were prepared against three different regions of RanBPM. All of them detected a 90 kDa protein that is predominantly localized both in the nucleus and in the cytoplasmic region surrounding the centrosome, but none of them stained the centrosome. In this context, our previous notion that RanBPM is a centrosomal protein should be discarded. RanBPM is well conserved in the animal kingdom. It may play an important role in uncovering Ran-dependent nuclear events.

Thrombin promotes fibroblast proliferation during the early stages of experimental radiation pneumonitis.

Huang, L., Ogushi, F., Tani, K., Ogawa, H., Kawano, T., Endo, T., Izumi, K., Ueno, J., Nishitani, H. and Sone, S. Thrombin Promotes Fibroblast Proliferation during the Early Stages of Experimental Radiation Pneumonitis. Radiat. Res. 156, 45-52 (2001). To clarify the role of thrombin in the pathogenesis of radiation-induced pneumonitis, we measured the thrombin activity and fibroblast growth-inducing activity in bronchoalveolar lavage fluid obtained from the irradiated lungs of rats at 1, 2, 4, 8 and 18 weeks after irradiation. Thrombin activity was not detected in the bronchoalveolar lavage fluid from unirradiated rats, but the bronchoalveolar lavage fluid from irradiated rats showed significantly increased thrombin activity which reached a maximum at 4 weeks after treatment. Higher fibroblast growth-inducing activity was detected in the bronchoalveolar lavage fluid from irradiated rats at 4 and 18 weeks than in fluid from unirradiated rats. Bronchoalveolar lavage fluid from irradiated rats that were pretreated with the thrombin inhibitors antithrombin III and argatroban showed significantly inhibited fibroblast growth-inducing activity and thrombin activity at 4 weeks. However, these thrombin inhibitors did not inhibit fibroblast growth-inducing activity in bronchoalveolar lavage fluid from irradiated rats at 18 weeks. Purified rat thrombin similarly induced proliferation of fibroblasts derived from irradiated and unirradiated rats. These findings suggest that thrombin may play an important role as a fibroblast growth-inducing factor during the early stages of radiation pneumonitis.

Localization of human airway trypsin-like protease in the airway: an immunohistochemical study.

Human airway trypsin-like protease (HAT) has been isolated from mucoid sputum of patients with chronic airway diseases. In order to clarify the cellular source of this novel protease in the human airway, we examined the localization of immunoreactive HAT in bronchial tissues obtained at surgery and fixed in 4% paraformaldehyde using an extremely sensitive immunohistochemical technique called a catalyzed signal amplification method and a monoclonal antibody against recombinant HAT. HAT immunoreactivity was demonstrated in cytoplasm of ciliated cells of bronchial epithelium and/or at the basal part of cilia. No positive reaction was found in submucosal glands or mast cells. The heterogeneous distribution of HAT immunoreactivity within the bronchial epithelium indicates that its expression might be changeable and that it might be closely related to the physiological status of the airway epithelium. Non-specific but intense reaction caused by endogenous avidin-binding activity (EABA) was selectively detected in submucosal glands, but was effectively blocked by successive treatments with avidin and biotin. These results indicate that HAT may be synthesized in the ciliated cells and that it may play some physiological roles within the epithelial layer and on the airway surface. It is necessary to keep in mind that some cells show strong EABA, especially when a highly sensitive immunohistochemical technique is applied.