Combining multiset resolution and segmentation for hyperspectral image analysis of biological tissues.

Hyperspectral images can provide useful biochemical information about tissue samples. Often, Fourier transform infrared (FTIR) images have been used to distinguish different tissue elements and changes caused by pathological causes. The spectral variation between tissue types and pathological states is very small and multivariate analysis methods are required to describe adequately these subtle changes. In this work, a strategy combining multivariate curve resolution-alternating least squares (MCR-ALS), a resolution (unmixing) method, which recovers distribution maps and pure spectra of image constituents, and K-means clustering, a segmentation method, which identifies groups of similar pixels in an image, is used to provide efficient information on tissue samples. First, multiset MCR-ALS analysis is performed on the set of images related to a particular pathology status to provide basic spectral signatures and distribution maps of the biological contributions needed to describe the tissues. Later on, multiset segmentation analysis is applied to the obtained MCR scores (concentration profiles), used as compressed initial information for segmentation purposes. The multiset idea is transferred to perform image segmentation of different tissue samples. Doing so, a difference can be made between clusters associated with relevant biological parts common to all images, linked to general trends of the type of samples analyzed, and sample-specific clusters, that reflect the natural biological sample-to-sample variability. The last step consists of performing separate multiset MCR-ALS analyses on the pixels of each of the relevant segmentation clusters for the pathology studied to obtain a finer description of the related tissue parts. The potential of the strategy combining multiset resolution on complete images, multiset segmentation and multiset local resolution analysis will be shown on a study focused on FTIR images of tissue sections recorded on inflamed and non-inflamed palatine tonsils.

Monitoring polymorphic transformations by using in situ Raman hyperspectral imaging and image multiset analysis.

Polymorphism is often encountered in many crystalline compounds. To control the quality of the products, it is relevant knowing the potential presence of polymorph transformations induced by different agents, such as light exposure or temperature changes. Raman images offer a great potential to identify polymorphs involved in a process and to accurately describe this kind of solid-state transformation in the surface scanned. As a way of example, this work proposes the use of multiset analysis on the series of Raman hyperspectral images acquired during a thermal induced transformation of carbamazepine as the optimal way to extract useful information about polymorphic or any other kind of dynamic transformation among process compounds. Image multiset analysis, performed by using Multivariate Curve Resolution-Alternating Least Squares (MCR-ALS), will furnish pure spectra and distribution maps of the compounds involved in the process and, hence, will allow the identification of polymorphs and, more important, the description of the process evolution at a global and local (pixel) level. Thus, process will be defined from a spatial point of view and by means of a set of global process profiles dependent on the process control variable. The results obtained confirm the power of this methodology and show the crucial role of the spatial information contained in the image (absent in conventional spectroscopy) for a correct process description.

[Antiangiogenic therapy in Sorsby's fundus dystrophy without a mutation in the TIMP-3 gene]. / Tratamiento antiangiogénico en fondo de distrofia de Sorsby sin mutación en gen de TIMP-3.

CASE REPORT: The case is presented of a 32-year-old man referring to metamorphopsia and blurred vision in both eyes for 3 days. Best corrected visual acuity of 20/32 in the right eye and 20/25 in the left eye. Fundus examination revealed the presence of drusen-like deposits, suggestive of Sorsby's fundus dystrophy (SFD) and choroidal neovascularization (CNV) bilaterally. The patient received intravitreal ranibizumab. Visual acuity improved to 20/20 in both eyes at 6-months follow-up, and results of fundus examination showed complete regression of neovascularization. No mutations were found in the TIMP-3 gene. DISCUSSION: The known mutations in TIMP-3 may not be extended to all patients with SFD. The use of intravitreal ranibizumab may be considered as a therapeutic option in CNV secondary to SFD.

Tratamiento antiangiogénico en fondo de distrofia de Sorsby sin mutación en gen de TIMP-3 / Antiangiogenic therapy in Sorsby's fundus dystrophy without a mutation in the TIMP-3 gene

Caso clínico: Varón de 32 años, con metamorfopsias y visión borrosa bilateral de tres días de evolución. Mejor agudeza visual corregida de 20/32 en OD y 20/25 en OI. La funduscopia presenta lesiones amarillentas difusas sugerentes de distrofia de Sorsby y membranas neovasculares (MNV). Recibió tratamiento con ranibizumab intravítreo, mejorando la agudeza visual a 20/20 en ambos ojos y remitiendo las MNV. No se hallaron mutaciones conocidas de TIMP-3. Discusión: Las mutaciones conocidas en TIMP-3 pueden no estar extendidas a todos los pacientes con fondo de distrofia de Sorsby. El ranibizumab intravítreo debe considerarse para el tratamiento de MNV secundaria a esta enfermedad (AU)

Case report: The case is presented of a 32-year-old man referring to metamorphopsia and blurred vision in both eyes for 3 days. Best corrected visual acuity of 20/32 in the right eye and 20/25 in the left eye. Fundus examination revealed the presence of drusen-like deposits, suggestive of Sorsby's fundus dystrophy (SFD) and choroidal neovascularization (CNV) bilaterally. The patient received intravitreal ranibizumab. Visual acuity improved to 20/20 in both eyes at 6-months follow-up, and results of fundus examination showed complete regression of neovascularization. No mutations were found in the TIMP-3 gene. Discussion: The known mutations in TIMP-3 may not be extended to all patients with SFD. The use of intravitreal ranibizumab may be considered as a therapeutic option in CNV secondary to SFD (AU)

Chemometric strategies to unmix information and increase the spatial description of hyperspectral images: a single-cell case study.

Hyperspectral images are analytical measurements that provide spatial and structural information. The spatial description of the samples is the specific asset of these measurements and the reason why they have become so important in (bio)chemical fields, where the microdistribution of sample constituents or the morphology or spatial pattern of sample elements constitute very relevant information. Often, because of the small size of the samples, the spatial detail provided by the image acquisition systems is insufficient. This work proposes a data processing strategy to overcome this instrumental limitation and increase the natural spatial detail present in the acquired raw images. The approach works by combining the information of a set of images, slightly shifted from each other with a motion step among them lower than the pixel size of the raw images. The data treatment includes the application of multivariate curve resolution (unmixing) multiset analysis to the set of collected images to obtain the distribution maps and spectral signatures of the sample constituents. These sets of maps are noise-filtered and compound-specific representations of all the relevant information in the pixel space and decrease the dimensionality of the original image from hundreds of spectral channels to few sets of maps, one per sample constituent or element. The information in each compound-specific set of maps is combined via a super-resolution post-processing algorithm, which takes into account the shifting, decimation, and point spread function of the instrument to reconstruct a single map per sample constituent with much higher spatial detail than that of the original image measurement.

Resolution and segmentation of hyperspectral biomedical images by multivariate curve resolution-alternating least squares.

MCR-ALS is a resolution method that has been applied in many different fields, such as process analysis, environmental data and, recently, hyperspectral image analysis. In this context, the algorithm provides the distribution maps and the pure spectra of the image constituents from the sole information in the raw image measurement. Based on the distribution maps and spectra obtained, additional information can be easily derived, such as identification of constituents when libraries are available or quantitation within the image, expressed as constituent signal contribution. This work summarizes first the protocol followed for the resolution on two examples of kidney calculi, taken as representations of images with major and minor compounds, respectively. Image segmentation allows separating regions of images according to their pixel similarity and is also relevant in the biomedical field to differentiate healthy from non-healthy regions in tissues or to identify sample regions with distinct properties. Information on pixel similarity is enclosed not only in pixel spectra, but also in other smaller pixel representations, such as PCA scores. In this paper, we propose the use of MCR scores (concentration profiles) for segmentation purposes. K-means results obtained from different pixel representations of the data set are compared. The main advantages of the use of MCR scores are the interpretability of the class centroids and the compound-wise selection and preprocessing of the input information in the segmentation scheme.

[Analysis of the reasons for consultation and dermatology care cost in a primary care site]. / Análisis de los motivos de consulta y de su coste en la asistencia dermatológica en un centro de Atención Primaria.

INTRODUCTION: The objective of the study was to the visits for esthetic reasons in an out-patient dermatology consultation and their cost and calculate the invoicing of these visits for a site other than the medical specialist consulted. METHOD: Prospective study in an out-patient dermatology clinic for 12 random days in February 2005. Endpoints of age, gender, diagnosis, cost per visit, cryotherapy and electrocoagulation were collected. Patients were divided into 3 groups: request for esthetic treatment (A), request for dermatology visit (B) and did not come (C). RESULTS: Group B was the largest, with 205 users (46 %), followed by C with 134/455 (29 %) and by A with 116/455 (25 %). In the latter group, the diagnoses were: seborrheic keratosis 39/455 (9 %), acrocordons 21/455 (5 %), remaining diagnoses (intradermal melanocytic nevi, cherry angioma, solar lentigos): 56/116 (11 %). The cost of these visits was 2,528. 8 euros in the 12 days analyzed and treatment of a subgroup of 85 patients (18.75 %) with cryotherapy or electrocoagulation increased it up to 5,043.80 euros. Estimated cost for one year would be 82,950 euros. Calculation of the invoicing for a non-public supplier site to the National Health Service would be: 8769.60 euros/month and 97,875 euros/year. If we add the treatments described, we go from 28,403.40 euros/month to 317,113.80 euros/year. CONCLUSIONS: These data and daily experience should make us think about the ethical consequences (do all the patients have to wait the same time?) as well as legal and collective ones (what type of dermatology do we want to specialize in?).

Análisis de los motivos de consulta y de su coste en la asistencia dermatológica en un centro de Atención Primaria / Analysis of the reasons for consultation and dermatology care cost in a primary care site

Introducción. El objetivo del presente estudio fue conocer las visitas por motivos estéticos en una consulta de dermatología ambulatoria y su coste y estimar la facturación que estas visitas supondrían a un centro proveedor diferente al Institut Català de la Salut (ICS). Método. Estudio prospectivo en una consulta de Dermatología ambulatoria durante 12 días aleatorios de febrero de 2005. Se recogieron variables de edad, sexo, diagnóstico, coste por visita, crioterapia y electrocoagulación. Se dividieron los pacientes en 3 grupos: demanda de tratamiento estético (A), demanda de visita dermatológica (B) y no acude (C). Resultados. El grupo B resultó el mayor, con 205 usuarios (46 %), seguido del C con 134/455 (29 %) y por el A con 116/455 (25 %). En este último grupo los diagnósticos fueron: queratosis seborreica 39/455 (9 %), acrocordones 21/455 (5 %), resto de diagnósticos (nevus melanocíticos intradérmicos, puntos rubí y lentigos solares) 56/116 (11 %). El coste de estas visitas fue de 2.528,8 euros en los 12 días analizados, y el tratamiento de un subgrupo de 85 pacientes (18,7 %) con crioterapia o electrocoagulación lo elevó hasta los 5.043,8 euros. El coste estimado para un año sería de 82.950 euros. La estimación de la facturación de un centro proveedor que no fuera de titularidad pública al Sistema Nacional de Salud (SNS) sería: 8.769,6 euros/mes y 97.875 euros/año. Si añadimos los tratamientos descritos, pasamos a 28.403,4 euros/mes y a 317.113,8 euros/año. Conclusiones. Estos datos y la experiencia diaria deben hacernos reflexionar sobre las consecuencias éticas (¿tienen que esperar todos los pacientes lo mismo?), jurídicas y colectivas (¿a qué tipo de dermatología queremos dedicarnos?)

Introduction. The objective of the study was to the visits for esthetic reasons in an out-patient dermatology consultation and their cost and calculate the invoicing of these visits for a site other than the medical specialist consulted. Method. Prospective study in an out-patient dermatology clinic for 12 random days in February 2005. Endpoints of age, gender, diagnosis, cost per visit, cryotherapy and electrocoagulation were collected. Patients were divided into 3 groups: request for esthetic treatment (A), request for dermatology visit (B) and did not come (C). Results. Group B was the largest, with 205 users (46 %), followed by C with 134/455 (29 %) and by A with 116/455 (25 %). In the latter group, the diagnoses were: seborrheic keratosis 39/455 (9 %), acrocordons 21/455 (5 %), remaining diagnoses (intradermal melanocytic nevi, cherry angioma, solar lentigos): 56/116 (11 %). The cost of these visits was 2,528. 8 euros in the 12 days analyzed and treatment of a subgroup of 85 patients (18.75 %) with cryotherapy or electrocoagulation increased it up to 5,043.80 euros. Estimated cost for one year would be 82,950 euros. Calculation of the invoicing for a non-public supplier site to the National Health Service would be: 8769.60 euros/month and 97,875 euros/year. If we add the treatments described, we go from 28,403.40 euros/month to 317,113.80 euros/year. Conclusions. These data and daily experience should make us think about the ethical consequences (do all the patients have to wait the same time?) as well as legal and collective ones (what type of dermatology do we want to specialize in?)