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PubMed1987

Computerized interactive morphometry in pathology: current instrumentation and methods.

This review is concerned with the current applications of interactive computerized morphometry for diagnostic applications. "Interactive" differs from fully automatic procedures in that the essential function of cell recognition is performed by a trained observer, assisted by a computerized instrument that performs all desirable measurement and processing tasks. This article describes the instrumental needs (video systems, computer, and specialized hardware) and interactive peripherals, in particular, high-resolution touch screens for most common and currently useful video analysis tasks. The authors describe a number of general instrumental procedures with widespread applications (point counting, tracing of contours, graphic standards of size and length, shape analysis, automatic edge detection). Diagnostic procedures are based on the generation of multiple data followed by either multivariate statistical analysis that allows diagnosis of individual cases or hierarchical algorithms. The best current application is the objective study of controversial or difficult cases; there is a possibility that in the future interactive computerized morphometry may become useful for the mass screening of cytologic specimens.

Analog-Digital Conversion↗

PubMed1992

MIPSY: real-time morphometry to quantify the time course of rapid epithelial restitution.

The gastrointestinal mucosa has the ability to repair itself rapidly following superficial mucosal injury by rapid epithelial restitution. The mechanism consists of cell migration and does not involve mitosis. This study reports the mechanisms of rapid epithelial restitution in the rabbit colon in vivo and in the human colon in vitro, describes a new computerized real-time morphometry system to investigate the time course of restitution and presents a new method to calculate the migration speed of epithelia during the repair process. Superficial mucosal damage to the rabbit colon in vivo was produced by luminal exposure to 100 mM HCl for 5 min (80% of mucosal surface), a comparable injury in the human colon in vitro was obtained by luminal exposure to 10 mM HCl for 10 min (96% of mucosal surface). After detachment of the damaged tissue the intact epithelial cells in the vicinity of the necrosis extended pseudopodia and migrated over the denuded basal lamina. The morphological appearance of rapid epithelial restitution was the same in the rabbit and the human, only the time course was postponed in the human. The time course of rapid restitution was assessed by a newly developed computerized morphometry system (MIPSY). When tissues were examined after various time points following acid damage, 61% of the mucosa were damaged in the rabbit after 1 h, 10% after 2 hs and 20% after 5 hs. In the human colon 85% of the mucosal surface were damaged after 2 hs and 20% 5 hs after the end of acid exposure.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1992

Nuclear morphometry of primary B cell thyroid lymphoma.

Thyroid lymphoma is usually distinguished from anaplastic thyroid carcinoma and from Hashimoto's thyroiditis by morphological and immunohistochemical assessment of tissue sections. Our objective was to assess the value of nuclear morphometry in the differential diagnosis of these conditions. Nuclear area measurements were performed on 10 cases of thyroid lymphoma using an IBAS 2000 Image Analyser and compared with similar measurements performed on 10 cases of Hashimoto's thyroiditis and 2 of anaplastic thyroid carcinoma. It was found that karyometry demonstrated differences between all three conditions, the cases of thyroiditis being distinguishable from lymphoma on the basis of mean nuclear area alone. Mean nuclear area for lymphomas was greater than for Hashimoto's thyroiditis and lower than for anaplastic carcinomas. The mean nuclear area also reflected the grade of lymphoma, with the exception of one case which had a large reactive T cell population. It is concluded that nuclear morphometry provides valuable information in the diagnosis and assessment of thyroid lymphomas.

Adult↗

PubMed1989

Common statistical errors in morphometry.

Morphometry is the quantitative measurement of morphological features. Data is usually obtained by probabilistic sampling techniques and is often markedly variable due to intrinsic variations in sampled specimens. Statistical analyses are required both to allow for and to control such variability. Care is needed in the analysis of morphometric data if false conclusions are to be avoided. Examination of any reasonably sized sample of publications in morphometry usually results in the detection of at least several common errors of statistical practice. Commonest errors involve statistics being carried out on untransformed percentage data, statistics on ratios, repeated multiple applications of tests designed for single comparisons, misuse of correlation and violations of statistical assumptions.

Analysis of Variance↗

PubMed1989

The value of morphometry and DNA flow cytometry in addition to classic prognosticators in superficial urinary bladder carcinoma.

In 80 patients with primary superficial bladder carcinoma Tumor Nodes Metastasis (TNM classification: stages Ta and T1) with adequate follow-up of at least four years, the value of selective nuclear morphometry and DNA flow cytometry on paraffin-embedded material in addition to classic prognosticators was assessed. Only the quantitative techniques appeared to be valuable predictors of new tumor occurrence. The recurrence rate in patients with large nuclei (mean nuclear area greater than 95 micron 2; n = 29) and in aneuploid cases (n = 30) was significantly higher (Wilcoxon: P = 0.05 and P = 0.0001) than in those with small nuclei (mean nuclear area less than = 95 micron 2; n = 51) and diploid cases (n = 50). The prevalence of large nuclei and aneuploidy also appeared useful to predict progressive recurrence, i.e., grade 3 or/and muscle invasive carcinoma (TNM classification: stages T2-T4) (chi-square: P less than 0.0001). Clinical follow-up showed that only 62.1% of the cases with large nuclei remained free of progressive recurrence, compared with 92.2% of those with small nuclei (Mantel-Cox: P less than 0.0001). For the aneuploid and diploid cases, these figures came to 53.3% and 98% (Mantel-Cox: P less than 0.0001). By multivariate analysis DNA ploidy was selected as the best discriminator. None of the classic prognosticators, including histologic grade, had additional prognostic value. Also, morphometry did not add to the prognosis prediction, which can be explained by the considerable overlapping between the prevalence of large nuclei and aneuploidy (24 of 29 and 30 cases, respectively). These findings practically suggest that patients presenting with superficial carcinoma with large nuclei (mean nuclear area greater than 95 microns 2) or aneuploid DNA values should be treated more aggressively.

Adult↗

PubMed1991

Cytometry and morphometry of malignant fibrous histiocytoma of the extremities. Prediction of metastasis and mortality.

Flow cytometry and nuclear morphometry were compared with traditional pathologic grading techniques for predicting the course of malignant fibrous histiocytoma of the extremities. Clinical, pathologic, and flow/morphometric variables from 53 cases were tested by Cox regression for prediction of distant recurrence and mortality. Tumor grading based on extent of tumor necrosis was a significant predictor for both disease-free survival (p = .014) and overall survival (p = .003). The fraction of nuclei in the S + G2M segment of DNA histograms was significant for disease-free survival (p = .007), and remained significant (p = .033) in a joint Cox model with necrosis-based grade (p = .004 for the bivariate model). Relative risk for recurrence varied nearly 10x between the 10th and 90th percentiles of grade and (S + G2M)1/2. Overall survival was predicted by a nuclear shape feature termed "R" (p = .000008), the casewise difference (residual) between expected and observed nuclear perimeter as a function of average Feret diameter. In a bivariate Cox model, relative risk of mortality varied 35x between the 10th and 90th percentiles of grade and R. Cytometric and morphometric data contain information about recurrence-free and overall survival beyond that available from more usual clinical and pathologic features. It seems likely that nuclear morphometry, in particular, will prove to be a useful aid for estimating the prognosis of patients with malignant fibrous histiocytoma of the extremities.

DNA, Neoplasm↗

PubMed1985

The prognostic value of morphometry in ovarian epithelial tumors of borderline malignancy.

A fully "blind" morphometric analysis was made of 20 ovarian epithelial tumors; 18 of these were of borderline malignancy, one was a well-differentiated adenocarcinoma and one had been categorized as "borderline? malignant?" Morphometry correctly identified the adenocarcinoma, which had proved fatal, and the two tumors of borderline malignancy that had directly led to the patients' deaths, as having a "poor" prognosis. One tumor thought to have a "poor" prognosis was associated with long-term survival, but the patient had received chemotherapy. All the patients whose tumors were morphometrically graded as having a "good" prognosis were alive and tumor-free at intervals ranging from 4 to 14 years. It is concluded that the predictive prognostic power of morphometry, when applied to ovarian epithelial tumors of borderline malignancy, is greater than that of unaided light microscopy.

Adenocarcinoma, Mucinous↗

PubMed1991

Normal cervical spine morphometry and cervical spinal stenosis in asymptomatic professional football players. Plain film radiography, multiplanar computed tomography, and magnetic resonance imaging.

Diagnosis of cervical spinal stenosis or instability rests on the objective findings depicted on static and dynamic radiographs. Before abnormal spinal morphometry can be determined, it is first necessary to establish normal values for the specific patient population being evaluated. Several studies have attempted to establish norms for plain film measurements of the cervical spine in children and adults, but few have applied consistent methods for generating precise measurements. The first part of this study established normal values for cervical spinal morphometry and segmental spinal motion in the elite athlete. The second part of this study determined the most accurate screening method for detecting cervical spinal stenosis. Three sagittal diameters of the cervical spinal canal were compared to determine which represented the smallest midline diameter on static and dynamic radiographs. The Torg ratio was also evaluated as a method to detect significant cervical spinal stenosis and was shown to have a high sensitivity but poor positive predictive value. The study clarified why the ratio yields a large number of false positive cases. From the results of this study, an algorithm has been developed for the evaluation of stenosis of the cervical spine in athletes.

Adult↗

PubMed1985

Quantitative morphometry of squamous cell hyperplasia of the larynx.

The histopathological diagnosis of squamous cell hyperplasia of the larynx is very subjective. Since morphometry is highly reproducible, this method was applied to routine processed slides of 45 such lesions to assess objectively the epithelial characteristics. In each case measurements of nuclei of 50 cells in the basal, intermediate, and superficial cell layers were carried out. The data were analysed statistically. The findings suggest that quantitative morphometry may be helpful for the histopathological classification of squamous cell hyperplasia of the laryngeal mucosa.

Cell Nucleus↗

PubMed1987

Abnormal intestinal permeability and jejunal morphometry.

The cellobiose and mannitol differential sugar test is a non-invasive investigation of small bowel permeability, in which urinary recoveries of cellobiose and mannitol after a hyperosmolar oral load are expressed as a ratio to give a permeability index. Changes in the cellobiose:mannitol ratio often occur in coeliac disease, but some patients with abnormal permeability have normal jejunums by routine microscopy. Using computed morphometry the perimeter:lamina propria area index of jejunal biopsy samples was measured and compared with the cellobiose:mannitol ratio in three groups of patients: (i) those with coeliac disease with villous atrophy; (ii) those with normal jejunums and sugar test results: and (iii) those with normal jejunums but abnormal sugar test results. In addition to the expected difference in perimeter:lamina propria area index between patients with coeliac disease and those with normal findings (p less than 0.001), the index was also abnormal in patients with normal jejunums but abnormal sugar test results: (p less than 0.001 compared with group 1) and (0.01 greater than p greater than 0.001 compared with group 2). There was a significant overall correlation between the perimeter:lamina propria area index and cellobiose:mannitol ratio (p = 0.001). This study shows that computed jejunal morphometry can identify patients with subtle morphological changes that are related to abnormal intestinal permeability.

Celiac Disease↗

PubMed1988

Use of morphometry in cytological preparations for diagnosing follicular non-Hodgkin's lymphomas.

Morphometric techniques were applied to cytocentrifuge smears from 27 patients with histologically confirmed follicular non-Hodgkin's lymphoma to determine the usefulness of this method in diagnosis. Analysis of quantitative data confirmed that most subtypes were classified correctly on the basis of the proportion of large cells, small cleaved, and large non-cleaved cells, and nuclear, nucleolar, and cytoplasmic features. Morphometry is a more objective and reproducible technique than manual cell counting methods, and the use of cytocentrifuge smears has several advantages compared with conventional histological sectioning. Data derived with the aid of morphometry may be of value in follow up clinicopathological studies.

Cell Count↗

PubMed1992

Ageing and duodenal morphometry.

Small bowel morphometry was studied in 25 subjects under the age of 70 years and 22 over the age of 70. There was no evidence of malabsorption or malnutrition in either group. Two distal duodenal endoscopic biopsy specimens were examined morphometrically. There were no significant correlations between age and areas of duodenal surface epithelium, crypts and lamina propria, heights of villi and surface epithelium, depth of crypts, crypt to villus ratio, number of intraepithelial lymphocytes, duodenal architecture, enterocytes, brush border and Brunner glands. Contrary to previous reports there was no evidence for a significant effect of age on proximal small bowel morphometry.

Aged↗

PubMed1989

Left and right ventricular myocardial morphometry in fetal, neonatal, and adult sheep.

This study has examined left (LV) and right ventricular (RV) myocardial morphometry in perfusion-fixed hearts of late-gestation sheep fetuses, neonatal lambs, and adult sheep. During development, myocyte size, intercapillary distance, and myocyte myofibrillar and mitochondrial volume densities increased, whereas capillary density, the myocyte-to-capillary ratio, and the myocyte matrix volume density decreased. RV myocytes were larger than LV myocytes in cross section in fetuses and 4-day-old lambs. LV and RV myocytes were of similar size in 7-day-old lambs. LV and RV myocytes were of larger in older lambs and adult sheep. Differences between LV and RV myocyte volume densities of myofibrils, mitochondria, and matrix were also observed in fetuses and young lambs. As well, variation in capillary size and density was apparent between ventricles in the fetal and neonatal periods. We conclude that, in the sheep heart, 1) LV and RV morphometric differences exist during fetal and postnatal development, 2) fetal LV and RV myocardial morphometry is consistent with an RV dominance in utero, 3) rapid growth of LV and RV myocytes occurs in the perinatal period, and 4) the relative size of LV and RV myocytes does not reflect a postnatal LV dominance until between 1 and 4 wk after birth.

Age Factors↗

PubMed1991

Aerosol-derived lung morphometry: comparisons with a lung model and lung function indexes.

This study evaluated the ability of aerosol-derived lung morphometry to noninvasively probe airway and acinar dimensions. Effective air-space diameters (EAD) were calculated from the time-dependent gravitational losses of 1-microns particles from inhaled aerosol boluses during breath holding. In 17 males [33 +/- 7 (SD) yr] the relationship between EAD and volumetric penetration of the bolus into the lungs (Vp) could be expressed by the linear power-law function, log (EAD) alpha beta log (Vp). Our EAD values were consistent with Weibel's symmetric lung model A for small airways and more distal air spaces. As lung volume increased from 57 to 87% of total lung capacity (TLC), EAD at Vp of 160 and 550 cm3 increased 70 and 41%, respectively. At 57% TLC, log (EAD) at 160 cm3 was significantly correlated with airway resistance (r = -0.57, P less than 0.0204) but not with forced expired flow between 25 and 75% of vital capacity. Log (EAD) at 400 cm3 was correlated with deposition of 1-micron particles (r = -0.73, P less than 0.0009). We conclude that aerosol-derived lung morphometry is a responsive noninvasive probe of peripheral air-space diameters.

Adult↗

PubMed1990

Potential of nuclear morphometry and volume-corrected mitotic index in grading transitional cell carcinoma of the urinary bladder.

The potential of nuclear morphometry and volume-corrected mitotic index (M/V index) in grading cases of transitional cell carcinoma of the urinary bladder was studied. 30 cases of bladder cancer including all three WHO grades were evaluated. Four investigators selected independently the most atypical field from paraffin sections, and one investigator measured the nuclear areas from these fields using the IBAS 1&2 image analyzer system. Following the same sampling rule, four investigators counted the mitotic figures per area of neoplastic tissue in the microscopic image at an objective magnification of X40. The mean nuclear areas covered values from 28.1 to 139.0 microns 2 (mean +/- SD 57.2 +/- 18.9). The total variance of measurements was 359.1 and the mean variance between corresponding fields 110.2 (about 30% of the total variation). The efficiency was evaluated by estimating the fraction of falsely classified cases. Instrumental morphometry of nuclear area in a three-grade system gave an efficiency of 79% and of 90%, in a two-grade system. The M/V index varied from 0 to 54 (mean +/- SD 12.3 +/- 10.9). The total variance was 119.8 and the methodological variance 15.5 (about 13% of total variance). In a three-grade system this would correspond to an efficiency of about 75%; in a two-grade system the efficiency would be 88%. The results suggest that nuclear area and M/V index estimates constitute efficient grading systems in bladder carcinoma.

Carcinoma, Transitional Cell↗

PubMed1986

Evaluation by scoring and computerized morphometry of lesions of early Mycoplasma pulmonis infection and ammonia exposure in F344/N rats.

To evaluate lesions of ammonia exposure and Mycoplasma pulmonis infection in gnotobiotic F344/N rats, groups of rats were inoculated with M. pulmonis, exposed to 76 micrograms/liter (100 parts per million) ammonia, or both, or served as controls. Six rats from each group were killed 3, 5, 7, and 9 days after inoculation and their respiratory organs prepared for histologic examination. Lesions were assessed by subjective scoring and computerized morphometry, and results obtained by the two methods were compared to assess agreement of results. Lesions were limited to the nasal passages. Ammonia exposure resulted in hyperplastic and degenerative changes in the anterior nasal epithelium. Lesions of mycoplasmosis were more severe in ammonia-exposed than unexposed rats, but qualitative differences in lesions were not apparent. Results of the two methods agreed in assessment of submucosal inflammatory cell accumulation. Epithelial lesions were difficult to evaluate by both methods in infected, ammonia-exposed rats. In evaluation of lesions of ammonia exposure alone, agreement was adequate. Both methods indicated that exudates were significantly greater in ammonia-exposed infected rats than in non-exposed infected rats. Thus, scoring and morphometry provided similar assessments of differences in lesion severity among the treatment groups.

Ammonia↗

PubMedDate not supplied

The clinical relevance of classification of squamous cell hyperplasia of the larynx by morphometry.

By means of morphometry, differentiation between the classes of laryngeal squamous cell hyperplasia can easily be performed, mutually (Kleinsasser's classification) and in comparison with normal epithelium. It is rather difficult, however, to distinguish between class II (hyperplasia and atypia) and class III (carcinoma in situ). In the group of class II lesions, two groups of patients could be differentiated: a prognostically favourable and an unfavourable group. When using a linear discriminant analysis, the two groups mentioned could be distinguished morphometrically. In histopathological examination, lesions classified as hyperplasia and atypia (class II), must also be examined with morphometry, because in this way the group at risk can be traced.

Biopsy↗

PubMed1977

Staining of muscle tissue for quantitative studies and automated morphometry.

Seventy-six staining tests were carried out of paraffin sections of human and animal muscle to find a suitable staining method for quantitative morphometry of muscle fibers. The results were evaluated under the light microscope, on black and white photomicrographs and on an image analysing computer, the Quantimet 720.A brilliant scarlet-phosphotungstic acid-tartrazine method is described and recommended for automated morphometry after additional testing on 140 sections of developing human muscle using the Quantiment 720.

Animals↗