Papers by Manuella Militaru
The present article represents a thorough study whose purpose is to test the acute toxicity of so... more The present article represents a thorough study whose purpose is to test the acute toxicity of some synbiotic products obtained by experiment, to find how and to what extent the balance of the intestinal microbiota of the Wistar rats has been disturbed after the antibiotherapy, as well as how the intestinal microbiota can be recovered by the administration of the
Journal of Comparative Pathology, 2010

The histopathologic examination of hepatic fibrosis remains the gold standard in routine diagnosi... more The histopathologic examination of hepatic fibrosis remains the gold standard in routine diagnosis of
hepatopathies in veterinary medicine. However, the visual evaluation of fibrosis is usually limited by the observer’s
capabilities. This paper aimed to present the applicability of fractal analysis as a quantitative method for evaluating
the liver fibrosis grading using accessible tools, compared to one of the semiquantitative methods used currently
in human histopathology, the METAVIR scoring system. Ovine liver histological sections taken from 22 slaughtered
lambs, Masson’s trichromestained, were analyzed using the METAVIR score as the semiquantitative method for
staging the liver fibrosis and inflammatory reaction, and the fractal dimension of collagen regions as a quantitative
method for fibrosis evaluation. The results show strong correlations between fibrosis and fractal dimension as the
statistics revealed that there is a significant difference between the presence of fibrosis and its absence (p<0.001).
Significant differences between the fractal dimensions corresponding to F1 and F2 fibrosis grades were observed
for the images aquired with objective lens 20×. The presence of inflammatory cells did not influenced the fractal
dimension of fibrosis. The Receiver Operating Characteristic (ROC) plot provided fair results for discriminating
F1 versus F2 fibrosis grades, with the area under the ROC curve of 0.79. The study showed significant differences
between the fractal dimension values of the liver tissue with different fibrosis grades, therefore, the fractal analysis
provides a useful complementary tool in the histological examination.
Journal of Comparative Pathology, 2012
Journal of Comparative Pathology, 2009
Journal of Comparative Pathology, 2010
Journal of Comparative Pathology, 2015

Journal of Comparative Pathology, 2010
Introduction: A 10-year-old female German shepherd dog was presented with a retrobulbar mass comp... more Introduction: A 10-year-old female German shepherd dog was presented with a retrobulbar mass compressing the eyeball. Histopathological examination showed differentiated seromucinous gland tissue, morphologically consistent with salivary gland. Materials and Methods: Biopsy samples were collected for microscopical examination, fixed in 10% neutral buffered formalin, dehydrated, embedded in paraffin wax, sectioned (4 mm) and stained with HE. For comparison, samples of normal salivary gland, lachrymal gland and third eyelid gland were studied. Results: Microscopical examination of the retrobulbar mass revealed seromucinous tubuloalveolar glands with predominance of a mucinous component and presence of intercalated and striated ducts. In some parts of the parenchyma, cystic dilatation of alveoli and ducts was observed. There were no signs of neoplastic changes. Conclusions: A diagnosis of salivary gland heterotopia in the retrobulbar space was made.
Journal of Comparative Pathology, 2010
Current Opinion in Biotechnology, 2011

Introduction: Semi-automatic taking and processing of histopathological pictures is spreading, bu... more Introduction: Semi-automatic taking and processing of histopathological pictures is spreading, but reliable diagnostic tools to match the procedure are yet to be confirmed. One of the most promising instruments for gauging pathological changes in the complex morphology of tissue is fractal analysis, already confirmed in human medicine.
Materials and Methods: Mammary tissue samples were collected from 62 dogs and cats. 1237 histology pictures were labeled for the presence/absence of features characteristic for carcinoma and adenoma in dogs, and, supplementary, for fibroadenomatous change in cats. A statistical evaluation was made for the relation of the histopathology labels with the fractal dimension of the chromatin regions (FDCR) extracted by picture segmentation. Tests based on FDCR were assessed by ROC (Receiver Operating Curve) analysis. Likelihood ratios for the presence of lesion were calculated.
Results: FDCR is a good discriminator for the presence/absence of tumour lesions in the mammary gland. The performance of a test based on FDCR to identify the presence of carcinoma in a histology picture is very good for dogs and excellent for cats. The potential benefits of using distinct structural/textural FDCRs were not confirmed.
Conclusions: Fractal analysis is a reliable tool for the identification of malign and benign lesions in histology pictures of mammary tissue in dogs and cats. The test based on the fractal dimension of the chromatin regions can be integrated in complex diagnostic procedures, either by means of reference ranges, or by Bayesian inference, using likelihood ratios for the presence of a specific lesion.

A model for evaluating the survival time for dogs and cats diagnosed with mammary gland
carcinom... more A model for evaluating the survival time for dogs and cats diagnosed with mammary gland
carcinoma was developed. First results are reported, based on data recorded for 74 patients, all
subject to mastectomy and some of them to adjuvant chemotherapy as well. Both statistical analysis
and an artificial neural network were used, integrating over 20 assumed prognostic factors,
provided by clinical, pathology, and other laboratory exams. The effective operation of the
statistical tools is illustrated, along with the relevant results emerging from training and validating
the neural network. Fractal dimension of chromatin regions in the histology pictures from the lesion
is identified among the top prognostic factors, along with tumour dimension, age, alanine
transaminase and creatinine serum levels, and white blood cells count at diagnostic time. A
significant impact on the survival time was also revealed for adjuvant chemotherapy, NSAID
treatment, and neutering.

5th International Conference Computational Mechanics and Virtual Engineering COMEC 2013 24- 25 October 2013, Braşov, Romania, ISSN 978-606-19-0225-5, Oct 24, 2013
An artificial neural network model was developed for providing an estimation of the survival time... more An artificial neural network model was developed for providing an estimation of the survival time for cancer patients. Data from 31 dogs and cats treated as oncologic patients was used for training and validating the network which used 28 elementary predictors selected from clinical and para-clinical, macroscopic pathology, and histology information. The network was optimized to avert the overfitting, which blocks the learning process. Among the techniques tested and illustrated are: random noise in synapses, automatic cloning of well performing neurons, extended learning with/without jitter, jogging of connection weights, freezing of weights and biases, pruning of less performing nodes, cross-validation and bootstrapping methods for the selection of training and validation data sets. Once overfitting is avoided, the model provides not only reliable predictions, but also an identification of the most effective predictors.

5th International Conference Computational Mechanics and Virtual Engineering COMEC 2013 24- 25 October 2013, Braşov, Romania, ISSN 978-606-19-0225-5, Oct 24, 2013
This study examines the hypothesis that the fractal dimension of chromatin regions in histologica... more This study examines the hypothesis that the fractal dimension of chromatin regions in histological pictures has a systematic and measurable variation when tumors emerge in a tissue. We used 194 histological pictures of healthy tissue and of tissue of the same nature with tumoral changes from 24 cases of dogs and cats treated for malignant and benign epithelial tumors: carcinoma, seminoma, adenoma, trichoblastoma, epitelioma. Fractal analysis was performed on pictures reduced to selected chromatin areas. Results indicate that for chromatin pictures at x40 magnification the fractal dimension is significantly increased when tumoral changes are present on more than 20% of the picture area. The largest effect on fractal dimension was identified for mammary gland carcinoma.
Along with traditional morfometry methods, fractal analysis is gaining ground by the year among c... more Along with traditional morfometry methods, fractal analysis is gaining ground by the year among complementary tools to be used in the pathology exam of tumors.This paper reviews key progress made lately in this line of research. Difficulties that came out in the process are highlighted, as well as new insights on how to overcome them. The recent leap forward in hardware and image processing software, along with growing success of automatic and adaptive learning methods are identified as significant strengths that suggest imminent acceptance of fractal analysis in regular pathology practice.

Scientific reports, 2015
Islets of Langerhans are fundamental in understanding diabetes. A healthy human pancreas from a d... more Islets of Langerhans are fundamental in understanding diabetes. A healthy human pancreas from a donor has been used to asses various islet parameters and their three-dimensional distribution. Here we show that islets are spread gradually from the head up to the tail section of the pancreas in the form of contracted or dilated islet routes. We also report a particular anatomical structure, namely the cluster of islets. Our observations revealed a total of 11 islet clusters which comprise of small islets that surround large blood vessels. Additional observations in the peripancreatic adipose tissue have shown lymphoid-like nodes and blood vessels captured in a local inflammatory process. Our observations are based on regional slice maps of the pancreas, comprising of 5,423 islets. We also devised an index of sphericity which briefly indicates various islet shapes that are dominant throughout the pancreas.
The present article represents a thorough study whose purpose is to test the acute toxicity of so... more The present article represents a thorough study whose purpose is to test the acute toxicity of some synbiotic products obtained by experiment, to find how and to what extent the balance of the intestinal microbiota of the Wistar rats has been disturbed after the antibiotherapy, as well as how the intestinal microbiota can be recovered by the administration of the
Journal of Biotechnology, 2015
Uploads
Papers by Manuella Militaru
hepatopathies in veterinary medicine. However, the visual evaluation of fibrosis is usually limited by the observer’s
capabilities. This paper aimed to present the applicability of fractal analysis as a quantitative method for evaluating
the liver fibrosis grading using accessible tools, compared to one of the semiquantitative methods used currently
in human histopathology, the METAVIR scoring system. Ovine liver histological sections taken from 22 slaughtered
lambs, Masson’s trichromestained, were analyzed using the METAVIR score as the semiquantitative method for
staging the liver fibrosis and inflammatory reaction, and the fractal dimension of collagen regions as a quantitative
method for fibrosis evaluation. The results show strong correlations between fibrosis and fractal dimension as the
statistics revealed that there is a significant difference between the presence of fibrosis and its absence (p<0.001).
Significant differences between the fractal dimensions corresponding to F1 and F2 fibrosis grades were observed
for the images aquired with objective lens 20×. The presence of inflammatory cells did not influenced the fractal
dimension of fibrosis. The Receiver Operating Characteristic (ROC) plot provided fair results for discriminating
F1 versus F2 fibrosis grades, with the area under the ROC curve of 0.79. The study showed significant differences
between the fractal dimension values of the liver tissue with different fibrosis grades, therefore, the fractal analysis
provides a useful complementary tool in the histological examination.
Materials and Methods: Mammary tissue samples were collected from 62 dogs and cats. 1237 histology pictures were labeled for the presence/absence of features characteristic for carcinoma and adenoma in dogs, and, supplementary, for fibroadenomatous change in cats. A statistical evaluation was made for the relation of the histopathology labels with the fractal dimension of the chromatin regions (FDCR) extracted by picture segmentation. Tests based on FDCR were assessed by ROC (Receiver Operating Curve) analysis. Likelihood ratios for the presence of lesion were calculated.
Results: FDCR is a good discriminator for the presence/absence of tumour lesions in the mammary gland. The performance of a test based on FDCR to identify the presence of carcinoma in a histology picture is very good for dogs and excellent for cats. The potential benefits of using distinct structural/textural FDCRs were not confirmed.
Conclusions: Fractal analysis is a reliable tool for the identification of malign and benign lesions in histology pictures of mammary tissue in dogs and cats. The test based on the fractal dimension of the chromatin regions can be integrated in complex diagnostic procedures, either by means of reference ranges, or by Bayesian inference, using likelihood ratios for the presence of a specific lesion.
carcinoma was developed. First results are reported, based on data recorded for 74 patients, all
subject to mastectomy and some of them to adjuvant chemotherapy as well. Both statistical analysis
and an artificial neural network were used, integrating over 20 assumed prognostic factors,
provided by clinical, pathology, and other laboratory exams. The effective operation of the
statistical tools is illustrated, along with the relevant results emerging from training and validating
the neural network. Fractal dimension of chromatin regions in the histology pictures from the lesion
is identified among the top prognostic factors, along with tumour dimension, age, alanine
transaminase and creatinine serum levels, and white blood cells count at diagnostic time. A
significant impact on the survival time was also revealed for adjuvant chemotherapy, NSAID
treatment, and neutering.
hepatopathies in veterinary medicine. However, the visual evaluation of fibrosis is usually limited by the observer’s
capabilities. This paper aimed to present the applicability of fractal analysis as a quantitative method for evaluating
the liver fibrosis grading using accessible tools, compared to one of the semiquantitative methods used currently
in human histopathology, the METAVIR scoring system. Ovine liver histological sections taken from 22 slaughtered
lambs, Masson’s trichromestained, were analyzed using the METAVIR score as the semiquantitative method for
staging the liver fibrosis and inflammatory reaction, and the fractal dimension of collagen regions as a quantitative
method for fibrosis evaluation. The results show strong correlations between fibrosis and fractal dimension as the
statistics revealed that there is a significant difference between the presence of fibrosis and its absence (p<0.001).
Significant differences between the fractal dimensions corresponding to F1 and F2 fibrosis grades were observed
for the images aquired with objective lens 20×. The presence of inflammatory cells did not influenced the fractal
dimension of fibrosis. The Receiver Operating Characteristic (ROC) plot provided fair results for discriminating
F1 versus F2 fibrosis grades, with the area under the ROC curve of 0.79. The study showed significant differences
between the fractal dimension values of the liver tissue with different fibrosis grades, therefore, the fractal analysis
provides a useful complementary tool in the histological examination.
Materials and Methods: Mammary tissue samples were collected from 62 dogs and cats. 1237 histology pictures were labeled for the presence/absence of features characteristic for carcinoma and adenoma in dogs, and, supplementary, for fibroadenomatous change in cats. A statistical evaluation was made for the relation of the histopathology labels with the fractal dimension of the chromatin regions (FDCR) extracted by picture segmentation. Tests based on FDCR were assessed by ROC (Receiver Operating Curve) analysis. Likelihood ratios for the presence of lesion were calculated.
Results: FDCR is a good discriminator for the presence/absence of tumour lesions in the mammary gland. The performance of a test based on FDCR to identify the presence of carcinoma in a histology picture is very good for dogs and excellent for cats. The potential benefits of using distinct structural/textural FDCRs were not confirmed.
Conclusions: Fractal analysis is a reliable tool for the identification of malign and benign lesions in histology pictures of mammary tissue in dogs and cats. The test based on the fractal dimension of the chromatin regions can be integrated in complex diagnostic procedures, either by means of reference ranges, or by Bayesian inference, using likelihood ratios for the presence of a specific lesion.
carcinoma was developed. First results are reported, based on data recorded for 74 patients, all
subject to mastectomy and some of them to adjuvant chemotherapy as well. Both statistical analysis
and an artificial neural network were used, integrating over 20 assumed prognostic factors,
provided by clinical, pathology, and other laboratory exams. The effective operation of the
statistical tools is illustrated, along with the relevant results emerging from training and validating
the neural network. Fractal dimension of chromatin regions in the histology pictures from the lesion
is identified among the top prognostic factors, along with tumour dimension, age, alanine
transaminase and creatinine serum levels, and white blood cells count at diagnostic time. A
significant impact on the survival time was also revealed for adjuvant chemotherapy, NSAID
treatment, and neutering.