Direct estimation of kinetic parametric images for dynamic PET.

Dynamic positron emission tomography (PET) can monitor spatiotemporal distribution of radiotracer in vivo. The spatiotemporal information can be used to estimate parametric images of radiotracer kinetics that are of physiological and biochemical interests. Direct estimation of parametric images from raw projection data allows accurate noise modeling and has been shown to offer better image quality than conventional indirect methods, which reconstruct a sequence of PET images first and then perform tracer kinetic modeling pixel-by-pixel. Direct reconstruction of parametric images has gained increasing interests with the advances in computing hardware. Many direct reconstruction algorithms have been developed for different kinetic models. In this paper we review the recent progress in the development of direct reconstruction algorithms for parametric image estimation. Algorithms for linear and nonlinear kinetic models are described and their properties are discussed

Inverse Problems in data-driven multi-scale Systems Medicine: application to cancer physiology

Systems Medicine is an interdisciplinary framework involving reciprocal feedback between clinical investigation and mathematical modeling/analysis. Its aim is to improve the understanding of complex diseases by integrating knowledge and data across multiple levels of biological organization. This Thesis focuses on three inverse problems, arising from three kinds of data and related to cancer physiology, at different scales: tissues, cells, molecules. The general assumption of this piece of research is that cancer is associated toa path ological glucose consumption and, in fact, its functional behavior can be assessed by nuclear medicine experiments using [18F]-fluorodeoxyglucose (FDG) as a radioactive tracer mimicking the glucose properties. At tissue-scale, this Thesis considers the Positron Emission Tomography (PET) imaging technique, and deals with two distinct issues within compartmental analysis. First, this Thesis presents a compartmental approach, referred to as reference tissue model, for the estimation of FDG kinetics inside cancer tissues when the arterial blood input of the system is unknown. Then, this Thesis proposes an efficient and reliable method for recovering the compartmental kinetic parameters for each PET image pixel in the context of parametric imaging, exploiting information on the tissue physiology. Standard models in compartmental analysis assume that phosphorylation and dephosphorylation of FDG occur in the same intracellular cytosolic volume. Advances in cell biochemistry have shown that the appropriate location of dephosphorylation is the endoplasmic reticulum (ER). Therefore, at cell-scale, this Thesis formalizes a biochemically-driven compartmental model accounting for the specific role played by the ER, and applies it to the analysis of in vitro experiments on FDG uptake by cancer cell cultures obtained with a LigandTracer (LT) device. Finally, at molecule-scale, this Thesis provides a preliminary mathematical investigation of a chemical reaction network (CRN), represented by a huge Molecular Interaction Map (MIM), describing the biochemical interactions occurring between signaling proteins in specific pathways within a cancer cell. The main issue addressed in this case is the network parameterization problem, i.e. how to determine the reaction rate coefficients from protein concentration data

Comparative overview of brain perfusion imaging techniques Epub

Background and Purpose - Numerous imaging techniques have been developed and applied to evaluate brain hemodynamics. Among these are positron emission tomography, single photon emission computed tomography, Xenon-enhanced computed tomography, dynamic perfusion computed tomography, MRI dynamic susceptibility contrast, arterial spin labeling, and Doppler ultrasound. These techniques give similar information about brain hemodynamics in the form of parameters such as cerebral blood flow or cerebral blood volume. All of them are used to characterize the same types of pathological conditions. However, each technique has its own advantages and drawbacks. Summary of Review - This article addresses the main imaging techniques dedicated to brain hemodynamics. It represents a comparative overview established by consensus among specialists of the various techniques. Conclusions - For clinicians, this article should offer a clearer picture of the pros and cons of currently available brain perfusion imaging techniques and assist them in choosing the proper method for every specific clinical setting

Voxel-level dosimetry of 177Lu-octreotate : from phantoms to patients

In radionuclide therapy, the patient is injected with relatively high amounts of therapeutic radiopharmaceutical which localises to target tissue and emits ionising radiation. Unfortunately, a perfectly targeting radiopharmaceutical has not been discovered and part of the radiopharmaceutical accumulates to healthy tissues, which are also thus irradiated. In order to ensure safe use, the absorbed dose of radiation-sensitive organs must be monitored. The focus of this thesis is on patient specific dosimetry of lutetium-177 (Lu-177) labelled somatostatin analogue Lu-177-DOTA-Tyr3-octreotate (Lu-177-DOTATATE) treatments and development of internal dosimetry software. Lu-177-DOTATATE is a radiopharmaceutical that binds to somatostatin receptors and is used to treat patients with metastatic neuroendocrine tumours. Recent studies have shown significant treatment outcome improvements with Lu-177-DOTATATE when compared to previously used somatostatin analogue treatments. However, the kidneys are the healthy organ which receives the highest amount of radiation dose from Lu-177-DOTATATE treatments and could be the organ that limits the number of treatments a patient can tolerate. In addition, absorbed dose to kidneys varies highly from patient to patient and thus patient specific dosimetry is recommended. Despite many years of dosimetry research and the existence of several published scientific dosimetry tools, there is no clinically validated kidney dosimetry software for Lu-177-DOTATATE treatments. The aim of this thesis was to study quantification accuracy of Lu-177 radionuclide using SPECT/CT imaging and to study mean absorbed doses to kidneys and dose distribution characteristics of Lu-177-DOTATATE. A streamlined voxel level absorbed dose software for clinical practice was developed and validated for kidney dosimetry of Lu-177-DOTATATE treatments. The effect of reconstruction methods on Lu-177 quantification accuracy was studied using an anthropomorphic phantom with known Lu-177 sources. Acquired data were reconstructed using different image compensation methods and results were compared with known source activities in the phantom. It was found that Monte Carlo simulation based scatter compensation and SPECT detector response compensation improved Lu-177 quantification accuracy considerably. Similar findings were also observed with data from patients treated with Lu-177-DOTATATE. A Monte Carlo simulation study was carried out to investigate absorbed dose distribution of Lu-177. Two main findings were that electrons emitted by Lu-177 can be assumed to absorb locally when the resolution of the imaging system is taken into account and the photon cross-irradiation can contribute significantly to total absorbed dose especially in the vicinity of highly active volumes. Using Lu-177-DOTATATE patient data, two different kidney absorbed dose calculation methods were compared. Comparing the mean kidney absorbed dose with the estimated maximum absorbed dose, it was observed that Lu-177-DOTATATE accumulates unevenly to kidney causing significantly heterogeneous dose distribution within kidneys. In addition, a simplified imaging protocol was found to be adequate for dosimetry purposes and was later adopted clinical practice. Combining previous findings new voxel level dosimetry software was developed. The clinical feasibility of the proposed software was tested with digital phantom simulations and reanalysing patient data from Lu-177-DOTATATE treatments. The software was found to be reliable and to speed up and simplify the dosimetry workflow.Lutetium-177 (Lu-177) -oktreotaattihoito on tehokas hoitomenetelmä levinneisiin neuroendokriinisiin kasvaimiin. Suonensisäisesti annettava Lu-177 -isotoopilla leimattu oktreotaatti sitoutuu kasvaimien pinnalla ilmeneviin somatostatiinireseptoreihin ja Lu-177:n emittoima elektronisäteily tuhoaa syöpäsolukkoa. Paikallisesti ionisoivan elektronisäteilyn lisäksi Lu-177 emittoi myös gammasäteilyä, joka voidaan kuvantaa gammakameralla potilaan ulkopuolelta. Oktreotaatti sitoutuu pieninä määrinä myös terveisiin kudoksiin. Sitoutumaton lääke erittyy munuaisten kautta virtsaan, minkä seurauksena munuaiset voivat saada hoidoista suuren säteilyannoksen. Tämä voi johtaa munuaisten vajaatoimintaan. Munuaisiin kertyvän radiolääkkeen määrä vaihtelee suuresti potilaiden välillä, minkä vuoksi munuaisiin kohdistuvaa säderasitusta tulee seurata potilaskohtaisesti. Tämän väitöskirjan tavoite oli kehittää annoslaskentaohjelma radionuklidihoitoihin keskittyen Lu-177 -oktreotaattihoitoihin. Työssä tutkittiin Lu-177 -aktiivisuuden määrityksen tarkkuutta SPECT-TT-kuvauksilla ja eri kuvarekonstruktiomenetelmien vaikutusta aktiivisuuden määrityksen suorituskykyyn. Monte Carlo -simuloinneilla tutkittiin Lu-177:n elektroni- ja gammasäteilyn annosjakaumia. Kliinisesti käytössä olevilla annoslaskentamenetelmillä vertailtiin Lu-177 -oktreotaattihoidettujen potilaiden munuaisannoksia ja annosten vaihtelua hoitokertojen välillä. Yhdistämällä näiden töiden tulokset kehitettiin uusi potilaan yksilöllisiin SPECT-TT-kuviin perustuva annoslaskentaohjelma. Työssä osoitettiin, että kuvarekonstruktiossa käytettävillä kompensaatiomenetelmillä on huomattava vaikutus Lu-177:n aktiivisuuden määrityksen tarkkuuteen etenkin pienten kohteiden kohdalla. Tarkimmat tulokset saavutettiin yhdistämällä kuvarekonstruktioon vaimennuskorjaus, sirontakorjaus ja kollimaattori-detektori-vastemallinnus. Monte Carlo -simulointien avulla havaittiin elektronisäteilyn kantaman olevan häviävän pieni verrattuna gammakameran erotuskykyyn. Tämän takia SPECT-kuviin perustuvassa Lu-177:n annoslaskennassa voidaankin olettaa elektronien absorboituvan paikallisesti. Toisaalta simuloinneissa havaittiin, että hyvin aktiivisista lähteistä aiheutuu suuri gammasäteilyannos, joka tulisi ottaa huomioon annoslaskennassa. Lu-177 -oktreotaattihoidettujen potilaiden munuaisten säteilyannokset vaihtelivat suuresti. Potilaskuvista määritetyistä annosjakaumista havaittiin, että munuaisten keskimääräinen annos ja maksimiannos erosivat toisistaan tilastollisesti merkitsevästi. Radionuklidihoitojen annoslaskenta on monivaiheinen prosessi, jossa SPECT-kuvaus- ja rekonstruktiomenetelmät ovat keskeisessä asemassa. Tämän lisäksi annoslaskenta- ja analyysimenetelmien tulee olla käyttötarkoitukseen validoituja. Väitöskirjassa esitetty annoslaskentaohjelma mahdollistaa potilaan yksilöllisiin SPECT-TT-kuviin perustuvan annoslaskennan. Ohjelma validoitiin Lu-177 -oktreotaattihoitojen munuaisannoksen määrittämiseen, mutta sen kehittäminen muiden radionuklidien annoslaskentaan on mahdollista. Ohjelmiston kehitys on tehty yhteistyössä HERMES Medical Solution -yrityksen kanssa ja ohjelma tulee kaupallisesti saataville

The influence of accurate attenuation correction on quantitative gamma camera imaging

Gamma camera systems are used in a variety of diagnostic applications to image and in some cases measure, the physiological uptake of a radioactive tracer within the body. A number of factors, particularly attenuation and scatter of photons within the body tissues can cause degradation of image quality and inaccuracies in the measurement of tracer uptake. Single photon emission tomography (SPECT) systems which incorporate an xray computed tomography (CT) facility have enabled accurate transmission images of the patient to be obtained. These ‘attenuation maps’ can be used to correct the SPECT images for the effects of attenuation. The aim of this project was to investigate the use of an x-ray CT based attenuation correction (AC) system in SPECT gamma camera imaging. The use of AC with other physical parameters of the imaging process including scatter was firstly examined in order to determine the optimum imaging parameters required to maximise image quality. The influence of attenuation, scatter and other imaging parameters on the accuracy of absolute and relative quantitative measurements was then investigated. The methodology involved using the GE Millenium Hawkeye gamma camera system to obtain images of a range of phantoms filled with various concentrations of radioactivity; from simple point sources to phantoms which simulate organs of the body. An attempt was made to establish SPECT sensitivity values that would allow accurate determination of activity in a region of interest. These sensitivity values were applied to all subsequent measurements and a measure made of quantitative accuracy. The results showed that the sensitivity value used for quantitative SPECT measurements must reflect the reconstruction method and corrections used in the acquisition. Attenuation correction proved to be more significant than scatter correction in quantitative accuracy, with activity results being within 30% of expected values in all cases where AC was used