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PubMed2005

TmaDB: a repository for tissue microarray data.

BACKGROUND: Tissue microarray (TMA) technology has been developed to facilitate large, genome-scale molecular pathology studies. This technique provides a high-throughput method for analyzing a large cohort of clinical specimens in a single experiment thereby permitting the parallel analysis of molecular alterations (at the DNA, RNA, or protein level) in thousands of tissue specimens. As a vast quantity of data can be generated in a single TMA experiment a systematic approach is required for the storage and analysis of such data. DESCRIPTION: To analyse TMA output a relational database (known as TmaDB) has been developed to collate all aspects of information relating to TMAs. These data include the TMA construction protocol, experimental protocol and results from the various immunocytological and histochemical staining experiments including the scanned images for each of the TMA cores. Furthermore the database contains pathological information associated with each of the specimens on the TMA slide, the location of the various TMAs and the individual specimen blocks (from which cores were taken) in the laboratory and their current status i.e. if they can be sectioned into further slides or if they are exhausted. TmaDB has been designed to incorporate and extend many of the published common data elements and the XML format for TMA experiments and is therefore compatible with the TMA data exchange specifications developed by the Association for Pathology Informatics community. Finally the design of the database is made flexible such that TMA experiments from several types of cancer can be stored in a single database, which incorporates the national minimum data set required for pathology reports supported by the Royal College of Pathologists (UK). CONCLUSION: TmaDB will provide a comprehensive repository for TMA data such that a large number of results from the numerous immunostaining experiments can be efficiently compared for each of the TMA cores. This will allow a systematic, large-scale comparison of tumour samples to facilitate the identification of gene products of clinical importance such as therapeutic or prognostic markers. In addition this work will contribute to the establishment of a standard for reporting TMA data analogous to MIAME in the description of microarray data.

Data Interpretation, Statistical↗

PubMed1994

Integrated clinical workstations for image and text data capture, display, and teleconsultation.

The Department of Veterans Affairs (VA) DHCP Imaging System digitally records clinically significant diagnostic images selected by medical specialists in a variety of hospital departments, including radiology, cardiology, gastroenterology, pathology, dermatology, hematology, surgery, podiatry, dental clinic, and emergency room. These images, which include true color and gray scale images, scanned documents, and electrocardiogram waveforms, are stored on network file servers and displayed on workstations located throughout a medical center. All images are managed by the VA's hospital information system (HIS), allowing integrated displays of text and image data from all medical specialties. Two VA medical centers currently have DHCP Imaging Systems installed, and other installations are underway.

Diagnostic Imaging↗

PubMed1996

Neurobiology of treatment-resistant schizophrenia: new insights and new models.

In an attempt to understand schizophrenia, four important fields have been implicated in the disease process and are reviewed here. Early findings that antipsychotic drugs were dopamine antagonists led to a dopaminergic theory of schizophrenia. However, it now appears that a primary dopaminergic abnormality is an unlikely explanation. The cortex has always been thought to be involved in the development of schizophrenia and recent data from neuropsychological, postmortem and imaging studies have indicated that connections between the prefrontal and temporolimbic areas within the brain may be abnormal. Traditionally, schizophrenia has been considered to be a disease with an adult onset pathology. This theory has now been challenged by data suggesting that in schizophrenia, anatomical changes in the adult brain are non-progressive and occurred prior to the onset of illness. Finally, studies on neuronal gene expression have indicated that all antipsychotic drugs modulate DNA transcription in the shell of the nucleus accumbens and that newer antipsychotics produce a quite different pattern of expression from conventional neuroleptics. These recent approaches provide new opportunities in the understanding of schizophrenia, its treatment and prevention.

Animals↗

PubMed2004

The pathology of ligamentum flavum in degenerative lumbar disease.

STUDY DESIGN: A pathologic study of the ligamentum flavum in degenerative lumbar disease. OBJECTIVES: To elucidate the clinical significance of each pathologic finding of the ligamentum flavum. SUMMARY OF BACKGROUND DATA: In many reports, researchers observed the ligamentum flavum removed partially during surgery and did not evaluate the whole image of the ligamentum flavum. In addition, there are only a few reports that examined the possible association between various histologic findings and clinical findings. And, thus, there are many unclear points in the clinical significance indicated by each pathologic finding. METHODS: The study participants were 50 patients with degenerative lumbar diseases who underwent surgical decompression with removal of the ligamentum flavum of the affected spinal level. Tissue specimens of the removed ligamentum flavum in cross section were prepared, and changes in the elastic fibers and collagen fibers were evaluated in three grades to evaluate the whole image. In addition, we observed the presence or absence of any focal lesions and statistically analyzed the possible association between these histologic findings and clinical symptoms or image findings. RESULTS: In regard to the association between histologic findings and clinical symptoms or image findings, calcification was observed in significantly older patients, who tended to have low scores in preoperative JOA score, and was frequently observed in patients with cauda equina symptoms. Patients with ossification had a significantly greater % slip, and chondroid cells were frequently observed in patients with spondylolisthesis. CONCLUSION: Various pathologic findings provided important foundations for discussing the pathogenesis of lesions in ligamentum flavum. Calcification was frequently observed in elderly patients and those with cauda equina symptoms, and these patients tended to have severer preoperative symptoms. Chondroid cells were frequently observed in patients with spondylolisthesis, and patients with ossification had a greater % slip, suggesting involvement of mechanical load in ossification of ligaments. The pathologic findings were significantly related to the clinical features, and these findings will be profitable for understanding the pathogenesis of degenerative lumbar disease.

Aged↗

PubMed2003

3-D reconstruction of the vestibular endorgans in pediatric temporal bones.

We investigated the vestibular endorgans in three children using 3-D reconstructions from histological sections. The right temporal bone of a newborn child without peripheral vestibular pathology was used as reference model and the temporal bones from a child with Goldenhar syndrome and a child with Pierre Robin sequence with known peripheral vestibular pathology were studied. All five temporal bones were prepared by the celloidin technique and sectioned at 20 microm. Each available section was digitized with a slide scanner. The imaging data were layered anatomically correctly and rendered in a 3-D software. With this technique all vestibular endorgans were reconstructed and measured. The standard deviations in distances ranged between 0.5 and 1.2% and in angles between 0.1 and 2.9 degrees. Both maculae were curved in the longitudinal and transverse axes which described a curve of approximately 35 degrees. The angles between the semicircular ducts varied between 97 and 110 degrees. The pathological models demonstrated a distorted configuration of the semicircular canals and differed substantially from the reference model in most of the measured distances and angles. The method presented is capable of generating 3-D models of the vestibular system from histological sections with an acceptable precision without previously inserted reference marks. Archival celloidin sections are widely available and will be an important resource in understanding the detailed 3-D geometry of the vestibular system which has not yet been accomplished.

Goldenhar Syndrome↗

PubMed2005

Pathology-guided MR analysis of acute and chronic experimental allergic encephalomyelitis spinal cord lesions at 1.5T.

PURPOSE: To directly correlate spinal cord pathology of guinea pigs with experimental allergic encephalomyelitis (EAE) to the MRI data obtained at 1.5T. MATERIALS AND METHODS: Spinal cords from EAE animals were imaged in vivo with the following MRI sequences: T2-FSE, PD-FSE, fluid-attenuated inversion recovery (FLAIR)-FSE, T2-CSE, T1-CSE, T1-CSE + gadolinium-DTPA (Gd-DTPA), PD-CSE, and short-tau inversion recovery (STIR)-FSE. The spinal cords were removed and the lesions with specific pathological compositions were identified by histological analysis. Regions of interest (ROIs) were drawn on the corresponding MR images, and signal-to-noise ratios (SNRs) were measured for each MR sequence and compared with controls. RESULTS: The receiver operating characteristic (ROC) analysis of STIR-FSE and PD-CSE was able to differentiate tissue that contained cellular infiltrates with a high degree of accuracy. The SNRs of T2-FSE, STIR-FSE, T2-CSE, PD-CSE, and T1-CSE + Gd-DTPA were elevated in lesions that contained cellular infiltrates alone, whereas the SNRs of PD-CSE and T1-CSE + Gd-DTPA were reduced in demyelinated lesions that also contained inflammation. CONCLUSION: The SNR difference between the two lesion groups suggests that the combination of STIR-FSE, PD-CSE, and T1-CSE + Gd-DTPA sequences may be useful for differentiating inflammatory lesions containing demyelination from lesions with inflammation alone.

Acute Disease↗

PubMed2003

Three subsequent single doses of gadolinium chelate for brain MR imaging in multiple sclerosis.

BACKGROUND AND PURPOSE: A triple-dose (TD) of gadolinium chelate is highly sensitive approach for detecting lesion activity in multiple sclerosis (MS). However, individual TD injections do not provide data on the severity of the pathologic process in a population of lesions, and its clinical use is limited by the cost-benefit considerations. Our aim was to determine whether the use of three subsequent single doses (SD) of a gadolinium chelate in brain MR imaging is useful in detecting MS lesions with different patterns of enhancement. METHODS: In 10 patients, T1-weighted spin-echo images were acquired before and after three intravenous administrations of 0.1 mmol/kg of gadodiamide. RESULTS: In all patients, SD images showed six enhancing lesions; double-dose (DD) images, 13; and TD images, 22. Differences between SD and TD and between DD and TD were significant (P <.018). Six lesions (27%) enhanced with all the three doses; seven (32%), with both DD and TD; and nine (41%), with only TD. Proportions of patients with at least one enhancing lesion were, for SD, four of 10; DD, seven of 10; and TD, nine of 10. In defining active disease in these nine patients, we needed only 19 SDs versus the 30 SDs that would have been needed if individual TD injections were used. CONCLUSION: With three subsequent SD injections, the number of enhancing lesions progressively increases. This approach allows the distinction of three levels of enhancement, and it reduces the amount of contrast agent needed to distinguish patients with active MS from those with nonactive MS.

Adult↗

PubMed2003

A methodology for generating normal and pathological brain perfusion SPECT images for evaluation of MRI/SPECT fusion methods: application in epilepsy.

Quantitative evaluation of brain MRI/SPECT fusion methods for normal and in particular pathological datasets is difficult, due to the frequent lack of relevant ground truth. We propose a methodology to generate MRI and SPECT datasets dedicated to the evaluation of MRI/SPECT fusion methods and illustrate the method when dealing with ictal SPECT. The method consists in generating normal or pathological SPECT data perfectly aligned with a high-resolution 3D T1-weighted MRI using realistic Monte Carlo simulations that closely reproduce the response of a SPECT imaging system. Anatomical input data for the SPECT simulations are obtained from this 3D T1-weighted MRI, while functional input data result from an inter-individual analysis of anatomically standardized SPECT data. The method makes it possible to control the 'brain perfusion' function by proposing a theoretical model of brain perfusion from measurements performed on real SPECT images. Our method provides an absolute gold standard for assessing MRI/SPECT registration method accuracy since, by construction, the SPECT data are perfectly registered with the MRI data. The proposed methodology has been applied to create a theoretical model of normal brain perfusion and ictal brain perfusion characteristic of mesial temporal lobe epilepsy. To approach realistic and unbiased perfusion models, real SPECT data were corrected for uniform attenuation, scatter and partial volume effect. An anatomic standardization was used to account for anatomic variability between subjects. Realistic simulations of normal and ictal SPECT deduced from these perfusion models are presented. The comparison of real and simulated SPECT images showed relative differences in regional activity concentration of less than 20% in most anatomical structures, for both normal and ictal data, suggesting realistic models of perfusion distributions for evaluation purposes. Inter-hemispheric asymmetry coefficients measured on simulated data were found within the range of asymmetry coefficients measured on corresponding real data. The features of the proposed approach are compared with those of other methods previously described to obtain datasets appropriate for the assessment of fusion methods.

Adult↗

PubMed1995

[Clinical and paraclinical diagnosis of AIDS neurologic lesions].

Seventy to eighty percent of HIV-infected patients exhibit neurological disorders at an advanced stage of the disease. In almost 90% of cases anatomical examination of brains shows histological lesions. Even when often reversible neurological disorders occur during the HIV primary infection, most of the manifestations of central nervous system (CNS) damage remains the prerogative of severe immunodepression. The principal CNS lesions associated with HIV infection are presented here with the clinical and biological elements that lead to the diagnosis. Cerebral toxoplasmosis holds a privileged place in these manifestations since it responds to an efficient curative and prophylactic treatment with a well-codified medical care based on the test treatment. Biological data, therefore, only have a contributing value. HIV encephalopathy is frequent, but the dementia syndrome is less frequent than the finding of associated imaging and pathological anatomy: atrophy and lesions of the white matter. Thus, the dementia complex is an elimination diagnosis. Cryptococcosis must be systematically considered, not only in patients with meningeal symptoms and headaches, but also with those with isolated fever. The demonstration of cryptococcus and cryptococcic antigen in the CSF has an almost absolute diagnostic value; imaging plays a very small diagnostic role, looking for an exceptional cryptococcoma. Multifocal progressive leukoencephalopathy benefits from the accuracy of MRI, and the diagnosis is usually based on clinical data, MRI and evidence of the virus in the CSF by PCR, even though the only mean of obtaining full proof is, in theory, stereotaxic biopsy. Primary cerebral lymphoma is the diagnostic alternative to toxoplasmosis.(ABSTRACT TRUNCATED AT 250 WORDS)

AIDS Dementia Complex↗

PubMed1991

Effects of prolonged transesophageal echocardiographic imaging and probe manipulation on the esophagus--an echocardiographic-pathologic study.

Transesophageal echocardiography is being increasingly utilized in the operating room and intensive care and ambulatory settings. However, to date no data are available concerning possible trauma of the transesophageal echocardiographic technique to the esophagus due to probe insertion, manipulation or direct ultrasound energy transmission. To test the hypothesis that transesophageal manipulations caused no traumatic or thermal injury to the esophageal mucosa, 12 animals were studied with continuous transesophageal echocardiography for a period of variable duration (mean 4.6 h +/- 51 min). The study group consisted of four monkeys (mean weight 5.7 +/- 0.6 kg and eight mongrel dogs (mean weight 29.8 +/- 1.4 kg). The eight dogs were studied during right heart bypass with full heparinization for 6.6 +/- 0.2 h, whereas the four monkeys were studied for 60 to 90 min in the absence of cardiopulmonary bypass and anticoagulation. Immediately after completion of transesophageal echocardiography in each case, the esophagus was entirely excised. Detailed macroscopic and microscopic examination of the esophagus revealed no significant mucosal or thermal injury. This preliminary animal study suggests that transesophageal echocardiography is safe for the esophageal mucosa in animals as small as 5 kg in weight, despite prolonged use and in the presence of systemic anticoagulation.

Animals↗

PubMed2006

[Cardiovascular whole-body MR imaging in patients with symptomatic peripheral arterial occlusive disease].

PURPOSE: To examine patients with peripheral-arterial-occlusive-disease (PAOD) for systemic effects associated with atherosclerosis using a comprehensive state-of-the-art whole-body MR examination protocol. The protocol comprises the assessment of the complete arterial vasculature (except coronary arteries), the brain, and the heart. MATERIALS AND METHODS: Multi-station whole-body 3D MR angiography was performed in sixty consecutive patients with clinical suspicion for PAOD at 1.5 T (Magnetom Avanto, Siemens, Erlangen, Germany). Functional and delayed enhancement cardiac images were acquired, as well as FLAIR images of the brain and TOF angiography of intracranial vessels. MR and DSA images were assessed by independent observers for atherosclerotic manifestations and other pathology. Sensitivity and specificity for the detection of vascular pathology was calculated for MR data using conventional DSA of the symptomatic region as standard-of-reference. RESULTS: Sensitivity and specificity for the detection of significant vascular stenosis (> 70 % luminal narrowing) was 94 % and 96 % (PPV 87 %, NPV 98 %). Significant microangiopathic tissue alterations (n = 7) and/or cerebral infarction (n = 18) were diagnosed in 23/60 patients. Thirty-eight of 60 patients presented with systolic left ventricular wall motion abnormalities. In 24 patients subendocardial or transmural delayed enhancement was detected in corresponding regions, indicating prior myocardial infarction. CONCLUSION: For patients with PAOD and suspected systemic atherosclerotic disease a comprehensive diagnosis of accompanying cardiovascular pathology and therefore staging of systemic atherosclerotic disease is feasible within one MR examination.

Aged↗

PubMed1989

Cognitive impairment in patients with clinically isolated lesions of the type seen in multiple sclerosis. A psychometric and MRI study.

This study reports the performance on psychometric tests of a group of 48 patients with clinically isolated lesions of the type seen in multiple sclerosis (optic neuritis, brainstem and cord lesions). The cognitive functions studied were: 'IQ deficit', verbal and visual memory, abstracting ability, visual and auditory attention, and naming ability. The presence of brain pathology was investigated by means of magnetic resonance imaging (MRI). A group of 46 patients with rheumatic and neurological conditions not known to cause brain disease was used for comparison. Normative MRI data were obtained from a group of 40 normal volunteers. An overall 'Cognitive Ability Index' was significantly worse in patients with clinically isolated lesions when compared with physically disabled controls. IQ deficit and defective auditory attention were the more severely affected parameters. These deficits were significantly correlated with the duration of neurological symptoms and with the degree of brain pathology detected by MRI.

Adult↗

PubMed1993

Comparative genetic approach to the study of body image of children from 4 to 14 years of age using the fairy tale of the ant.

This work was designed to study the body image of 3 groups of normal children (ns = 40) whose ages were 4 to 14 years with the assistance of a new projective technique, the tale of the ant from Royer. The data provide partial validation of this new procedure. Indicators of normal and pathological answers are given. Directions for research are suggested.

Adolescent↗

PubMed1996

Quantitative DNA ploidy analysis of breast carcinoma: a study of the effects of joint photographer experts group (JPEG) compression on DNA ploidy images.

Telepathology usage in the past has typically been a qualitative procedure rather than a quantitative measurement. DNA ploidy using image analysis has been favorably compared to DNA ploidy analysis by flow cytometry in numerous publications. A step from DNA ploidy analysis using conventional image analysis to DNA ploidy analysis using stored images allows DNA ploidy analysis by image cytometry to become a powerful tool in telepathology. Remote DNA ploidy analysis using stored images has an impact on the field of pathology, as not every hospital or laboratory can afford to perform this type of specialized testing. However, images have large data files and require lengthy transmission times over communication systems to other computers. Joint Photographer Experts Group (JPEG) compression is a computer algorithm that allows the file size of an image to be reduced in order to decrease transmission times to another computer. A study was initiated to investigate the effects of JPEG compression on images of Feulgen stained breast tumor touch preps and the resulting DNA ploidy histograms.

Animals↗

PubMed2000

Histogram-based characterization of healthy and ischemic brain tissues using multiparametric MR imaging including apparent diffusion coefficient maps and relaxometry.

Decreased, renormalized, or increased values of the calculated apparent diffusion coefficient (ADC) are observed in stroke models. A quantitative description of corresponding tissue states using ADC values may be extended to include true relaxation times. A histogram-based segmentation is well suited for characterizing tissues according to specific parameter combinations irrespective of the heterogeneity found for human healthy and ischemic brain tissues. In a new approach, navigated diffusion-weighted images and ADC maps were incorporated into voxel-based parameter sets of relaxation times (T1, T2), and T1- or T2-weighted images, followed by a supervised histogram-based analysis. Healthy tissues were segmented by incorporating T1 relaxation into the data set, ischemic regions by combining T2- or diffusion-weighted images with ADC maps. Mean values of healthy and pathologic tissues were determined, spatial distributions of the parameter vectors were visualized using color-encoded overlays. One to six days after stroke, ischemic regions exhibited reduced relative mean ADC values.

Adult↗

PubMed2005

Fiberoptic ductoscopy findings in women with and without spontaneous nipple discharge.

BACKGROUND: Fiberoptic ductoscopy (FD), which allows direct visualization of the breast ductal lumen, is performed in women with and without spontaneous nipple discharge (SND). Previous reports suggested that cytologic evaluation of SND may be falsely interpreted as containing malignancy. The purpose of the current study, which was performed prospectively, was to determine whether ductoscopic findings were different in women with versus without SND, and to assess the implications of the differences in SND versus non-SND samples regarding the role of FD in assessing whether a woman has breast carcinoma. METHODS: Data were collected on the distance traveled by the ductoscope, visual observations, pathology, cytology, epithelial and foam cell quantity, and image analysis for ploidy, hypertetraploidy, and S-phase fraction. RESULTS: Of 100 FD specimens, 60 were from breasts without SND and 40 were from breasts with SND. Intraductal visual observations (P < or = 0.0002), pathologic findings in the resected specimen (P < or = 0.001), and quantity of epithelial cells (P=0.03) were influenced by the presence or absence of SND. Although one specimen from a benign breast was interpreted as cytologically malignant, every breast with both malignant cytology and aneuploidy contained cancer cells. A model incorporating cytology and SND was 92% sensitive and 60% specific in predicting which women had breast carcinoma. CONCLUSIONS: There were pronounced differences in FD samples from women with and without SND. FD biologic parameters can be chosen to optimize breast carcinoma predictive sensitivity and specificity. SND cytology can present a diagnostic problem, suggesting the need for histologic confirmation before the initiation of therapy.

Adult↗

PubMed1980

Developmental and psychodynamic issues related to cases of childhood functional hearing loss.

The literature is scant regarding the details of the personality organizations of children exhibiting functional hearing losses. Projective data gleaned from five clinical cases of childhood functional hearing loss is presented. The core pathology involves a poorly consolidated image of the self. Threats to the continuity and cohesiveness of the self are avoided through a form of selective inattention.

Adolescent↗

PubMed2005

Laparoscopic specimen extraction: morcellation.

OBJECTIVES: To review our experience with intact extraction and morecellation of nephrectomy specimen, and the advantages and disadvantages of morcellation indicated by current reports. PATIENTS AND METHODS: In a previous study, 56 consecutive patients undergoing radical and simple transperitoneal laparoscopic nephrectomy were prospectively evaluated. Morcellation specimens (33) were extracted at the umbilical or lateral port sites and intact specimens (23) through an infraumbilical incision. Data were obtained on pathology, narcotic requirements, hospital stay, complications, estimated blood loss, size of renal mass based on preoperative imaging, specimen weight and extraction incision length. RESULTS: The mean incision length was 1.2 cm in the morcellation group and 7.1 cm in the intact group (P< 0.001). There were no significant differences in pain or recovery between the groups. In two cases of tumor nephrectomy, microscopic invasion of the perinephric adipose tissue in the intact specimen group were up-staged from clinical T1 to pT3a disease; there was no change in patient treatment based on this information. CONCLUSIONS: With proper technique, morcellation is safe for extracting renal tumours. The specimen can be evaluated for histology but not for pathological staging, limiting its use with transitional cell carcinoma. Port-site seeding is rare, and does not appear to be more frequent than with open nephrectomy. Although morcellation is cosmetically more desirable, there was no significant advantage in operating time, pain or duration of hospital stay. The choice od extraction method depends on the surgeon's preference and patient choice.

Adolescent↗