[show abstract][hide abstract] ABSTRACT: We address the performance evaluation practices for developing medical image analysis methods, in particular, how to establish and share databases of medical images with verified ground truth and solid evaluation protocols. Such databases support the development of better algorithms, execution of profound method comparisons, and, consequently, technology transfer from research laboratories to clinical practice. For this purpose, we propose a framework consisting of reusable methods and tools for the laborious task of constructing a benchmark database. We provide a software tool for medical image annotation helping to collect class label, spatial span, and expert's confidence on lesions and a method to appropriately combine the manual segmentations from multiple experts. The tool and all necessary functionality for method evaluation are provided as public software packages. As a case study, we utilized the framework and tools to establish the DiaRetDB1 V2.1 database for benchmarking diabetic retinopathy detection algorithms. The database contains a set of retinal images, ground truth based on information from multiple experts, and a baseline algorithm for the detection of retinopathy lesions.
Computational and Mathematical Methods in Medicine 01/2013; 2013:368514. · 0.79 Impact Factor
[show abstract][hide abstract] ABSTRACT: Adiponectin is an adipocyte-expressed protein that regulates the glucose, lipid, and energy metabolism via adiponectin receptors 1 and 2. Obesity is a known risk factor for age-related macular degeneration (AMD). We, therefore, examined associations of single nucleotide polymorphisms in Adiponectin (ADIPOQ) and Adiponectin receptors 1 and 2 (ADIPOR1 and ADIPOR2) genes with the prevalence of advanced AMD in Finnish population. Thirty-seven markers for ADIPOQ, ADIPOR1 and ADIPOR2 were genotyped in a sample collection of 91 men and 177 women having exudative AMD and 18 men and 26 women having severe atrophic AMD. Patients were diagnosed by fundus photographs and fluorescein angiography. The control group (no signs of AMD in fundus photographs) consisted of 55 men and 111 women. Inclusion criteria age was over 65 years old without diabetes diagnosis. Out of the tested SNPs, rs10753929 located in intron of ADIPOR1 gene was significantly associated (p=0.0471) with AMD status when using a permutation procedure that controlled for the number of tested genotypes and genetic models. Odds ratio (OR) for the association was 1.699 (95% CI 1.192-2.423). The SNP consists of C/T alleles and the risk allele T had a minor allele frequency (MAF) of 20.4%. Distribution of proportion of cases/controls between alleles revealed an additive genetic model. Our findings reveal that rs10753929 ADIPOR1 variant is a novel candidate for AMD genetic risk factor in Finnish population.
[show abstract][hide abstract] ABSTRACT: A gabaergic antiepileptic drug, vigabatrin (VGB), is known to induce bilateral concentric visual field defects (VFD) in 30-40% of treated patients. Although the clinical and electrophysiological features of VFDs are well documented, the mechanism of retinal toxicity is still unclear.
To determine if low basal ornithine-δ-aminotranspherase (OAT) activity is implicated in the etiology of VGB retinotoxicity, resulting in a phenotype of a mild form of gyrate atrophy.
Assays of OAT activity in lymphocytes and GABA-transaminase activity in platelets were performed, and plasma levels of GABA, ornithine, lysine, glutamic acid and glutamine were measured, and visual fields were examined. A total of 47 subjects, aged 14-78 years, were examined. Twenty-one epileptic patients were off VGB more than 1 year; 11 patients with VGB-induced VFD and 10 with normal visual fields. Ten epileptic patients were on current VGB therapy more than 1 year; four patients with VGB-induced VFD and six with normal visual fields. The results were compared with those of 10 epilepsy patients taking tiagabine and six patients who suffered from gyrate atrophy (GA) or were obligate carriers of the disease.
In patients who had stopped VGB and who had VFDs, OAT activity was significantly reduced as compared with those who had normal visual fields (77.4pmol P5C/min/mgPro vs. 181.9pmol P5C/min/mgPro, p=0.002). In patients with ongoing VGB therapy, no difference was found between the patients with and without VFDs (149.4pmol P5C/min/mgPro vs. 159.1pmol P5C/min/mgPro).
: The results suggest that VGB retinotoxicity might be associated with elevated retinal ornithine mediated by low basal OAT activity.
Epilepsy research 11/2010; 92(1):48-53. · 2.48 Impact Factor
[show abstract][hide abstract] ABSTRACT: The pathogenesis of age-related macular degeneration (AMD) essentially involves chronic oxidative stress, increased accumulation of lipofuscin in retinal pigment epithelial (RPE) cells and extracellular drusen formation, as well as the presence of chronic inflammation. The capacity to prevent the accumulation of cellular cytotoxic protein aggregates is decreased in senescent cells which may evoke lipofuscin accumulation into lysosomes in postmitotic RPE cells. This presence of lipofuscin decreases lysosomal enzyme activity and impairs autophagic clearance of damaged proteins which should be removed from cells. Proteasomes are another crucial proteolytic machine which degrade especially cellular proteins damaged by oxidative stress. This review examines the cross-talk between lysosomes, autophagy and proteasomes in RPE cell protein aggregation, their role as a possible therapeutic target and their involvement in the pathogenesis of AMD.
Frontiers in bioscience (Elite edition) 01/2010; 2:1374-84.
[show abstract][hide abstract] ABSTRACT: Urocanic acid (UCA) is a major ultraviolet (UV)-absorbing endogenous chromophore in the epidermis and is also an efficacious immunosuppressant. The anti-inflammatory and cytoprotective effects of cis-UCA were studied in ocular surface cell cultures exposed to UV-B irradiation.
Human corneal epithelial cells (HCE-2) and human conjunctival epithelial cells (HCECs) were incubated with 10, 100, 1,000, and 5,000 microg/ml cis-UCA with and without a single UV-B irradiation dose. The concentrations of IL-1beta, IL-6, IL-8, and TNF-alpha in the culture medium and caspase-3 activity in the cell extract sampled were measured by enzyme-linked immunosorbent assay (ELISA). Cell viability was measured by the colorimetric MTT (3-(4,5-dimethyldiazol- 2-yl)-2,5-diphenyltetrazolium bromide) assay.
UV-B irradiation multiplied interleukin IL-6 and IL-8 secretion levels in HCE-2 cells and HCECs as analyzed with ELISA. Cell viability as measured by the MTT assay declined by 30%-50% in HCE-2 cells and by 20%-40% in HCECs after UV-B irradiation. Moreover, UV-B increased caspase-3 activity in both cell types as analyzed with ELISA. Treatment with 100 microg/ml cis-UCA completely suppressed IL-6 and IL-8 secretion, decreased caspase-3 activity, and improved cell viability against UV-B irradiation. No significant effects on IL-6 or IL-8 secretion, caspase-3 activity, or viability of the non-irradiated cells were observed with 100 microg/ml cis-UCA in both cell types. The 5,000 microg/ml concentration was toxic.
These findings indicate that cis-UCA may represent a promising anti-inflammatory and cytoprotective treatment option to suppress UV-B-induced inflammation and cellular damage in human corneal and conjunctival epithelial cells.
[show abstract][hide abstract] ABSTRACT: In this study, spectral images of 66 human retinas were collected. These spectral images were measured in vivo from 54 voluntary
diabetic patients and 12 control subjects using a modified ophthalmic fundus camera system. This system incorporates the optics
of a standard fundus microscope, 30 narrow bandpass interference filters ranging from 400 to 700 nanometers at 10 nm intervals,
a steady-state broadband lightsource and a monochrome digital charge-coupled device camera. The introduced spectral fundus
image database will be expanded in the future with professional annotations and will be made public.
[show abstract][hide abstract] ABSTRACT: Two problems especially important for supervised learning and classification in medical image processing are addressed in
this study: i) how to fuse medical annotations collected from several medical experts and ii) how to form an image-wise overall
score for accurate and reliable automatic diagnosis. Both of the problems are addressed by applying the same receiver operating
characteristic (ROC) framework which is made to correspond to the medical practise. The first problem arises from the typical
need to collect the medical ground truth from several experts to understand the underlying phenomenon and to increase robustness.
However, it is currently unclear how these expert opinions (annotations) should be combined for classification methods. The
second problem is due to the ultimate goal of any automatic diagnosis, a patient-based (image-wise) diagnosis, which consequently
must be the ultimate evaluation criterion before transferring any methods into practise. Various image processing methods
provide several, e.g., spatially distinct, results, which should be combined into a single image-wise score value. We discuss
and investigate these two problems in detail, propose good strategies and report experimental results on a diabetic retinopathy
database verifying our findings.
[show abstract][hide abstract] ABSTRACT: Diabetic retinopathy (DR) represents a common complication of type 2 diabetes mellitus. Appearance of DR lesions such as microaneurysms, haemorrhages, hard and soft exudates, IRMA and neovascularisation reflect the severity of DR. The aim of our study was to investigate the association of selected glycaemic parameters with particular DR abnormalities and their characteristics in patients with type 2 diabetes.
Eighty-three middle-aged patients with newly diagnosed type 2 diabetes mellitus participated in this 10-year prospective study. The glycaemic parameters such as glycated haemoglobin A1c (HbA1c), fasting blood/plasma glucose as well as 1- and 2-hour post-load glucose values were recorded at baseline, 5-year and 10-year follow-up. The fundus photographs were taken at baseline and then at 5-year and 10-year follow-ups and used for quantitative evaluation.
Statistically significant positive correlations were found between all investigated 5-year glucose values and the extent of DR lesions at 10-year follow-up (p < 0.003). The 1- and 2-hour post-load glucose values correlated with the DR lesions with the highest significance (p <or= 0.001). There were also associations between glycaemia and DR lesions investigated in a cross-sectional manner at 10-year follow-up. Binary logistic regression revealed that all glycaemic parameters at 5-year examination predicted the development of DR at 10-year follow-up (p <or= 0.001). The most powerful predictor of DR was the 2-hour post-load glucose value, since it explained almost 50% of DR cases.
Five-year blood glucose values predict the amount of DR lesions at 10-year follow-up in patients with recently diagnosed type 2 diabetes. The 2-hour post-load glucose at 5-year measurement appears to be the most reliable parameter predicting 10-year DR lesions.
Albrecht von Graæes Archiv für Ophthalmologie 12/2008; 247(3):335-41. · 1.93 Impact Factor
[show abstract][hide abstract] ABSTRACT: Accurate diagnosis, especially in progressive hereditary diseases, is essential for the treatment and genetic counseling of the patient and the family. Neuronal ceroid lipofuscinoses (NCL) are amongst the most common groups of neurodegenerative diseases. Infantile, juvenile, and adult-onset types with multiple genotype-phenotype associations have been described. A fluorimetric enzyme assay for palmitoyl protein thioesterase (PPT) from leukocytes and fibroblasts has been previously developed to confirm the diagnosis of infantile NCL. We describe a patient with juvenile-onset NCL phenotype with a new CLN1 mutation and deficient PPT activity. Over 40 different mutations have been found in patients with PPT deficiency, indicating that screening for known mutations is not an efficient way to diagnose this disorder. Therefore, PPT enzyme analysis should precede mutation analysis in suspected PPT deficiency, particularly in patients with granular osmiophilic deposits (GROD) or in patients who have negative ultrastructural data. The use of enzyme assay led to the diagnosis of this patient with juvenile-onset Finnish variant NCL with PPT deficiency, and we expect that greater awareness of the utility of the enzymatic assay may lead to identification of other similar cases awaiting a definitive diagnosis.
European Journal of Neurology 05/2007; 14(4):369-72. · 4.16 Impact Factor
[show abstract][hide abstract] ABSTRACT: For a particularly long time, automatic diagnosis of diabetic retinopathy from digital fundus images has been an active research topic in the medical image processing community. The research interest is justified by the excellent potential for new products in the medical industry and significant reductions in health care costs. However, the maturity of proposed algorithms cannot be judged due to the lack of commonly accepted and representative image database with a verified ground truth and strict evaluation protocol. In this study, an evaluation methodology is proposed and an image database with ground truth is described. The database is publicly available for benchmarking diagnosis algorithms. With the proposed database and protocol, it is possible to compare different algorithms, and correspondingly, analyse their maturity for technology transfer from the research laboratories to the medical practice.
Proceedings of the British Machine Vision Conference 2007, University of Warwick, UK, September 10-13, 2007; 01/2007
[show abstract][hide abstract] ABSTRACT: The purpose of the study was to determine whether the use of a GABAergic antiepileptic drug (AED), tiagabine, affects color vision and contrast sensitivity. Twenty newly diagnosed patients with partial epilepsy (aged 19-72 years), receiving tiagabine as their initial monotherapy for 5-41 months were examined. Color vision was examined with the Standard Pseudoisochromatic Plates 2 (SPP2), with the Farnsworth-Munsell 100 Hue Test (FM100) and with the Color Vision Meter 712 (CVM) anomaloscope. Contrast sensitivity was measured with the Pelli-Robson letter chart. Three patients excluded from the color vision evaluation for congenital red-green color vision defects. Seven out of 17 patients (41%) had acquired color vision deficit examined with the FM100. The CVM anomaloscope revealed minor defects in two patients. Contrast sensitivity function was within normal ranges. The present study suggests that AED therapy with tiagabine, like with other established and newer AEDs may interfere with color perception.
Epilepsy Research 01/2006; 67(3):101-7. · 2.24 Impact Factor
[show abstract][hide abstract] ABSTRACT: To investigate whether initial valproate (VPA) monotherapy for the treatment of epilepsy causes visual field defects and visual dysfunction.
In a cross-sectional study, visual fields were examined with the kinetic Goldmann and automated Humphrey perimeters, contrast sensitivity function with the Pelli-Robson letter chart and colour vision with the Standard Pseudoisochromatic Plates Part 2 (SPP 2) and Farnsworth-Munsell 100 Hue test (FM 100) in eighteen epilepsy patients (aged 18--50 years, 30.2.+/-10 years, mean+/-S.D.) treated with initial valproate monotherapy for 2--20 years (8.4+/-5.1 years).
None had vigabatrin-type, concentric visual field defect with the kinetic Goldmann or automated Humphrey perimetries. In the Humphrey perimetry, the mean deviation for the group was within normal limits varying from -2.53 to 0.59 dB (-0.74+/-0.80 dB) in the right eye and from -2.66 to 0.67 dB (-0.78+/-0.82 dB) in the left eye. In the FM 100 test, acquired colour vision deficiency was found in two out of 18 patients (11%, 95% CI: 0--25%). However, the mean total error score was lower in the patient group than in the control group. All patients had normal contrast sensitivity function.
The use of VPA in the treatment of epilepsy is not associated with visual field defects similar to vigabatrin, but may induce abnormalities in colour vision.
[show abstract][hide abstract] ABSTRACT: Vigabatrin (VGB) is an important treatment option for infantile spasms. Vigabatrin-induced visual field defects are at present the most important safety issue in the use of the drug. The knowledge concerning VGB-associated visual dysfunction in pediatric patients, particularly in those who have been exposed to VGB in utero is limited. We explored ophthalmic and neurologic findings in two children who have been exposed prenatally to VGB.
Epilepsy Research 07/2005; 65(1-2):117-20. · 2.24 Impact Factor
[show abstract][hide abstract] ABSTRACT: For a particularly long time, automatic diagnosis of diabetic retinopathy from dig- ital fundus images has been an active research topic in the medical image process- ing community. The research interest is justified by the excessive potential for new products in the medical industry and possible reductions in healthcare costs. How- ever, the maturity of state-of-the-art algorithms cannot be judged due to the lack of commonly accepted and representative image database with a verified ground truth and strict evaluation protocol. In this study, problems and issues related to the database are discussed from medical, image processing, and security perspectives. Based on the discussion, an evaluation methodology is proposed and a prototype image database with the ground truth is described. The database is made pub- licly available for benchmarking diagnosis algorithms. By utilizing the proposed database, it is now possible compare different algorithms, and correspondingly, analyze their maturity for technology transfer from the research laboratories to the medical practice.