L’imaging clinico è largamente usato ai giorni nostri per fornire informazioni anatomiche, fisiologiche e metaboliche, ma generalmente non è in grado di fornire informazioni in merito ai sottostanti processi biologici legati a patologie. Recentemente l’attenzione si è spostata verso lo studio dei processi molecolari che regolano l’interazione tra differenti parti biologiche che contribuiscono al sistema complessivo. Questa nuova branca della medicina molecolare chiamata Imaging Molecolare usa sonde con elevate specificità per fornire informazioni molto dettagliate. Il suo scopo è quello di fornire informazioni sui processi molecolari portando diagnosi sempre più precoci. L’Imaging Molecolare ha il vantaggio di identificare segni di malattie nel loro stadio iniziale cioè quando modifiche a livello fisiologico o anatomico non hanno ancora avuto luogo. Diagnosi tempestive danno la possibilità di ridurre notevolmente le dosi dei trattamenti medici e allo stesso tempo di ridurre al minimo gli effetti collaterali. Inoltre l’Imaging Molecolare permette di sviluppare sistemi di monitoraggio in tempo reale per massimizzare la cura e controllare in modo efficace gli effetti della stessa. Esempi di applicazioni sono lo studio dei tumori, dei sistemi neurologico, cardiovascolare e respiratorio. All’interno delle tecniche di Imaging Molecolare quella Ottica riveste un ruolo molto importante. Fino a pochi anni fa, il contributo dovuto allo scattering ha reso impossibile implementare sistemi ottici per questi studi. Infatti il potere di penetrazione della luce all’interno di tessuti biologici era limitato a qualche centinaia di micron. Recentemente è stata sviluppata una tecnologia chiamata Optical Projection Tomography (OPT) in grado di superare tali impedimenti e di studiare campioni dello spessore anche di qualche centimetro come insetti, embrioni e interi organi di animali ad alta risoluzione e in modalità ex-vivo. Le applicazioni dell’OPT spaziano da analisi anatomiche e istologiche a studi di espressioni geniche e persino a studi di fenomeni infiammatori legati a particolari malattie. L’OPT funziona in linea di principio come la tomografia assiale computerizzata (TAC) ma anziché far uso di radiazione X utilizza quella luminosa approssimativamente nello spettro del visibile. L’OPT è in grado di studiare fenomeni di fluorescenza che sono legati più che ad informazioni anatomiche a quelle funzionali. In quest’ultimo caso la tecnica di ricostruzione è più complessa e più simile alla SPECT (single positron emission computed tomography) che alla TAC.
Clinical imaging is largely used nowadays to provide anatomical, physiological or metabolical information but it cannot generally inform on the underlying molecular aberrations of the different diseases. Recently the attention has shifted towards investigating the molecular functions present in whole living systems focusing instead on the visualization of the molecular processes which regulate the interaction between the different biological parts that contribute to complex systems. This new Molecular Medicine branch, called Molecular imaging, exploits probes with high specificity and has the potential to provide more detailed information. Surface receptors, enzymes or structural proteins are the probes’ targets that are used in order to achieve true molecular imaging. They are employed with the ambitious goal of gaining information on several distinct molecular processes, leading to both early detection and staging of diseases. Moreover Molecular imaging can promote tailoring of targeted therapies for individual patients. The advantage of using Molecular imaging techniques resides in the fact that it makes possible to look into early disease signs which are commonly not detectable by others medical imaging modalities. In fact anatomical and physiological modifications reveal just late disease information, making the disease treatments much harder. At the same time an early stage disease diagnosis allows for very small doses administrations or expositions minimizing the cure side-effects; by way of molecular imaging, it will be possible to implement a real-time patient’s therapy response monitoring leading to a tailor-made and maximal efficiency cure design. Examples of application of Molecular imaging techniques are cancer, neurological, cardiovascular and respiratory diseases. Within the Molecular imaging techniques the Optical ones have recently increased in importance due to the overcoming of limiting technology hurdles. In fact tipical imaging is a key tool for the progress of biological sciences allowing for longitudinal unperturbed imaging of different biomarkers. Until recent years optical scattering contributions made impossible the implementation of optical imaging methodologies for the study of samples thicker than a few hundreds microns limiting their possible applications at the cellular level or for very small organisms’ investigations. Unfortunately the price to pay in exchange of the deeper penetration is a substantial decrease in resolution. Optical projection tomography (OPT) is a recently introduced new imaging technique which allows to image small biological samples, such as small insects, embryos, or whole small animals organs ex vivo and at high resolution. Its applications span from anatomical and histological analysis to tissue proteins expression and distribution, from developmental biology to gene functions and recently to inflammation disease studies. One of the most significant features of OPT is its capability to image small biological samples up to a few centimeters in size with unprecedented resolution. To obtain such a degree of resolution, the samples under investigation are made optically transparent through a chemical clearing process. In this way its scattering and absorption properties are highly reduced, making the light diffusive contribution negligible. The sample is then illuminated with a light beam and absorption or fluorescence signal is acquired in transillumination mode by a CCD camera. Projection images of the cleared sample are taken in an X-CT analogue fashion and the reconstruction mathematical problem, at least for the case of absorption projections, can be solved in a similar fashion using the parallel beam filtered back projection algorithm. Fluorescence tomographic absorption reconstructions utilize instead a Born normalized method that relies on a normalized transillumination approach.
Image processing and speed-up improvement for real time Optical Projection Tomography: applications for high throughput ex -vivo lung and heart inflammatory diseases imaging in different mice models
FUMENE FERUGLIO, Paolo
2010-01-01
Abstract
Clinical imaging is largely used nowadays to provide anatomical, physiological or metabolical information but it cannot generally inform on the underlying molecular aberrations of the different diseases. Recently the attention has shifted towards investigating the molecular functions present in whole living systems focusing instead on the visualization of the molecular processes which regulate the interaction between the different biological parts that contribute to complex systems. This new Molecular Medicine branch, called Molecular imaging, exploits probes with high specificity and has the potential to provide more detailed information. Surface receptors, enzymes or structural proteins are the probes’ targets that are used in order to achieve true molecular imaging. They are employed with the ambitious goal of gaining information on several distinct molecular processes, leading to both early detection and staging of diseases. Moreover Molecular imaging can promote tailoring of targeted therapies for individual patients. The advantage of using Molecular imaging techniques resides in the fact that it makes possible to look into early disease signs which are commonly not detectable by others medical imaging modalities. In fact anatomical and physiological modifications reveal just late disease information, making the disease treatments much harder. At the same time an early stage disease diagnosis allows for very small doses administrations or expositions minimizing the cure side-effects; by way of molecular imaging, it will be possible to implement a real-time patient’s therapy response monitoring leading to a tailor-made and maximal efficiency cure design. Examples of application of Molecular imaging techniques are cancer, neurological, cardiovascular and respiratory diseases. Within the Molecular imaging techniques the Optical ones have recently increased in importance due to the overcoming of limiting technology hurdles. In fact tipical imaging is a key tool for the progress of biological sciences allowing for longitudinal unperturbed imaging of different biomarkers. Until recent years optical scattering contributions made impossible the implementation of optical imaging methodologies for the study of samples thicker than a few hundreds microns limiting their possible applications at the cellular level or for very small organisms’ investigations. Unfortunately the price to pay in exchange of the deeper penetration is a substantial decrease in resolution. Optical projection tomography (OPT) is a recently introduced new imaging technique which allows to image small biological samples, such as small insects, embryos, or whole small animals organs ex vivo and at high resolution. Its applications span from anatomical and histological analysis to tissue proteins expression and distribution, from developmental biology to gene functions and recently to inflammation disease studies. One of the most significant features of OPT is its capability to image small biological samples up to a few centimeters in size with unprecedented resolution. To obtain such a degree of resolution, the samples under investigation are made optically transparent through a chemical clearing process. In this way its scattering and absorption properties are highly reduced, making the light diffusive contribution negligible. The sample is then illuminated with a light beam and absorption or fluorescence signal is acquired in transillumination mode by a CCD camera. Projection images of the cleared sample are taken in an X-CT analogue fashion and the reconstruction mathematical problem, at least for the case of absorption projections, can be solved in a similar fashion using the parallel beam filtered back projection algorithm. Fluorescence tomographic absorption reconstructions utilize instead a Born normalized method that relies on a normalized transillumination approach.
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