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A small-scale dosimetry model of the liver tissue

Stenvall, Anna (2012)
Medical Physics Programme
Abstract (Swedish)
Att behandla tumörsjukdomar genom injektion av radioaktiva läkemedel är en behandlingsteknik kallad radionuklidterapi. Det radioaktiva läkemedlet består av en radioaktiv isotop, fäst på en målsökande bärarmolekyl, specifik för den vävnad vari man önskar att läkemedlet skall ansamlas. Då den radioaktiva isotopen sönderfaller sänds joniserande strålning ut; strålning med förmågan att jonisera molekyler i den vävnad den sänds ut. Jonisering av vävnad kan medföra skador på DNA i cellkärnan, vilket kan leda till att cellen slutar fungerar, eller till och med dör. För en tumörcell är detta ett önskvärt resultat; selektiv, lokal och målsökande strålbehandling.

Då strålningen från en radioaktiv isotop sänds ut i ett medium kommer den att på... (More)
Att behandla tumörsjukdomar genom injektion av radioaktiva läkemedel är en behandlingsteknik kallad radionuklidterapi. Det radioaktiva läkemedlet består av en radioaktiv isotop, fäst på en målsökande bärarmolekyl, specifik för den vävnad vari man önskar att läkemedlet skall ansamlas. Då den radioaktiva isotopen sönderfaller sänds joniserande strålning ut; strålning med förmågan att jonisera molekyler i den vävnad den sänds ut. Jonisering av vävnad kan medföra skador på DNA i cellkärnan, vilket kan leda till att cellen slutar fungerar, eller till och med dör. För en tumörcell är detta ett önskvärt resultat; selektiv, lokal och målsökande strålbehandling.

Då strålningen från en radioaktiv isotop sänds ut i ett medium kommer den att på olika sätt växelverka med materian, varpå strålningen genom energiavgivning till mediet kommer att bromsas in och så småningom absorberas. Denna energiavgivning är den bakomliggande orsaken till joniseringen av mediet, varpå en ökad energideponering ökar antalet inträffade skador på DNA. Ett mått på denna energideponering anges som deponerad energi per massenhet och anges i enheten gray [Gy] och kallas absorberad dos.

Att beräkna den absorberade dosen är av intresse för att kunna optimera radionuklidterapin och således minska bieffekterna av stålningen på den friska vävnaden. Då den absorberade energin inuti en levande vävnad är en storhet som inte går att mäta, måste en beräkning genomföras för att erhålla en uppskattning av den absorberade dosen. Grunden för storheten absorberad dos är deponering av emitterad energi, en deponering som beror på de emitterade partiklarnas transport genom ett medium. Denna transport kan inte enkelt beräknas analytiskt, utan måste med hjälp av ett datorprogram, ett så kallat Monte Carlo program, simuleras fram.
Simulering av partiklars väg genom ett medium kräver en datormodell som beskriver dess geometri. De konventionella modellerna för att beräkna absorberad dos i mänskliga organ använder sig av en mycket förenklad bild av vävnaden, vilket leder till en osäker beräkning av den absorberade dosen. Syftet med detta projekt var att konstruera en mer noggrann modell av levervävnaden, för att på cellnivå kunna bestämma den absorberade dosen och således öka förståelsen för den absorberade dosens samband med den biologiska effekten.

Nya radionuklidbehandlingar har under de senaste åren introducerats i den kliniska verksamheten, behandlingar där mycket höga aktiviteter levereras för att uppnå absorberade doser höga nog för gott behandlingsresultat. Riskanalysen för frisk vävnad blir således än viktigare, varpå vikten av att kunna utföra rimligen adekvata absorberade dosberäkningar på en liten skala är stor.

I detta arbete har en realistisk modell av levervävnadens cellulära struktur skapats, baserad på morfologin av leverns funktionella enhet. Modellen kan således användas till att beräkna lokalt absorberade doser till de enskillda levercellerna, en absorberad dosberäkning mer detaljerad än den medelabsorberade dos vilken levereas med dagens beräkningsmodeller. (Less)
Abstract
Introduction: There is a need of reassessment of radiation absorbed dose specification in nuclear medicine, taking the non-uniformities in the distribution of radioactivity into account. This is especially important in radionuclide therapies where very high activities are administered and the radionuclides emit alpha particles, beta particles or low-energy electron and will require absorbed dose calculations on a scale comparable to the ranges of these particles. Although the liver is relatively radioresistant, this treatment rationale for radionuclide therapy has made the liver to be one of the dose-limiting organs. In this work we developed a small-scale dosimetry model of the liver, for Monte Carlo calculations of detailed and more... (More)
Introduction: There is a need of reassessment of radiation absorbed dose specification in nuclear medicine, taking the non-uniformities in the distribution of radioactivity into account. This is especially important in radionuclide therapies where very high activities are administered and the radionuclides emit alpha particles, beta particles or low-energy electron and will require absorbed dose calculations on a scale comparable to the ranges of these particles. Although the liver is relatively radioresistant, this treatment rationale for radionuclide therapy has made the liver to be one of the dose-limiting organs. In this work we developed a small-scale dosimetry model of the liver, for Monte Carlo calculations of detailed and more accurate absorbed dose distributions of the liver microstructure.

Material and method: The mathematical model created, based on the microstructure of the hepatic lobule, is used to calculate absorbed doses on a tissue level for different radionuclides and for different source-target combinations within the liver. The Monte Carlo codes MCNP5, Version 1.51 and MCNPX 2.6 were used to create the model, consisting of a close packed hexagonal lattice pattern representing the hepatic lobules with the edge length of 500 μm, each centered around the central vein and in the periphery framed by six portal triads; i.e. the portal vein, the hepatic artery and the bile duct. The lobule section consists mainly of the hepatocytes, the bile canaliculi, the space of Disse and the mononuclear phagocytosis system, i.e. the Kupffer cells. Absorbed energy for different common radionuclides; 125I, 90Y, 211At, 99Tcm, 111In, 177Lu, 131I and 18F were in different structures tallied and absorbed dose ratios between absorbed dosed in different targets and the mean absorbed dose to the total volume were calculated.

Results: Depending on the particles emitted and their energy the absorbed dose in different microstructures will differ. For nuclides emitting low energy particles, e.g. 125I, the ratio between the locally absorbed dose and the mean dose the whole organ will be high; in the Kupffer cell acting as source about 135 times whereas in the hepatocytes close to the source the absorbed dose is close to the mean dose but significantly lower in areas between the Kupffer cells. For 90Y on the other hand, the absorbed dose ratio in all target regions will be close to 1. For 111In, used in diagnostics, the absorbed dose ratio will be quite comparable to 177Lu, commonly used for the therapy. For the central vein, a possible target for radiation induced liver disease; the absorbed dose ratio will be as lowest for 177Lu whereas the use of 90Y and 18F will result in an absorbed dose close to the mean dose.

Discussion: The small-scale dosimetry model created is a simplification of the organization of the hepatic microstructure and therefore the results will visualize an idealized situation and the numerical values presented may not represent the biological reality. Since the dose-response relation of the non-uniform absorbed dose distribution for different commonly used radionuclides is not known, the biological implications still need to be investigated.

Conclusion: A heterogeneous activity distribution will for some radionuclides result in a non-uniform absorbed dose distribution. Compared to the mean absorbed dose to the total volume of the liver, both over- and under-estimations of the absorbed dose can be seen, results which can have implications both in outcome of radionuclide therapies and for radiation risk estimations. (Less)
Please use this url to cite or link to this publication:
author
Stenvall, Anna
supervisor
organization
year
type
H2 - Master's Degree (Two Years)
subject
language
English
id
3327129
date added to LUP
2012-12-20 19:08:34
date last changed
2013-09-05 12:23:06
@misc{3327129,
  abstract     = {Introduction: There is a need of reassessment of radiation absorbed dose specification in nuclear medicine, taking the non-uniformities in the distribution of radioactivity into account. This is especially important in radionuclide therapies where very high activities are administered and the radionuclides emit alpha particles, beta particles or low-energy electron and will require absorbed dose calculations on a scale comparable to the ranges of these particles. Although the liver is relatively radioresistant, this treatment rationale for radionuclide therapy has made the liver to be one of the dose-limiting organs. In this work we developed a small-scale dosimetry model of the liver, for Monte Carlo calculations of detailed and more accurate absorbed dose distributions of the liver microstructure.

Material and method: The mathematical model created, based on the microstructure of the hepatic lobule, is used to calculate absorbed doses on a tissue level for different radionuclides and for different source-target combinations within the liver. The Monte Carlo codes MCNP5, Version 1.51 and MCNPX 2.6 were used to create the model, consisting of a close packed hexagonal lattice pattern representing the hepatic lobules with the edge length of 500 μm, each centered around the central vein and in the periphery framed by six portal triads; i.e. the portal vein, the hepatic artery and the bile duct. The lobule section consists mainly of the hepatocytes, the bile canaliculi, the space of Disse and the mononuclear phagocytosis system, i.e. the Kupffer cells. Absorbed energy for different common radionuclides; 125I, 90Y, 211At, 99Tcm, 111In, 177Lu, 131I and 18F were in different structures tallied and absorbed dose ratios between absorbed dosed in different targets and the mean absorbed dose to the total volume were calculated.

Results: Depending on the particles emitted and their energy the absorbed dose in different microstructures will differ. For nuclides emitting low energy particles, e.g. 125I, the ratio between the locally absorbed dose and the mean dose the whole organ will be high; in the Kupffer cell acting as source about 135 times whereas in the hepatocytes close to the source the absorbed dose is close to the mean dose but significantly lower in areas between the Kupffer cells. For 90Y on the other hand, the absorbed dose ratio in all target regions will be close to 1. For 111In, used in diagnostics, the absorbed dose ratio will be quite comparable to 177Lu, commonly used for the therapy. For the central vein, a possible target for radiation induced liver disease; the absorbed dose ratio will be as lowest for 177Lu whereas the use of 90Y and 18F will result in an absorbed dose close to the mean dose.

Discussion: The small-scale dosimetry model created is a simplification of the organization of the hepatic microstructure and therefore the results will visualize an idealized situation and the numerical values presented may not represent the biological reality. Since the dose-response relation of the non-uniform absorbed dose distribution for different commonly used radionuclides is not known, the biological implications still need to be investigated.

Conclusion: A heterogeneous activity distribution will for some radionuclides result in a non-uniform absorbed dose distribution. Compared to the mean absorbed dose to the total volume of the liver, both over- and under-estimations of the absorbed dose can be seen, results which can have implications both in outcome of radionuclide therapies and for radiation risk estimations.},
  author       = {Stenvall, Anna},
  language     = {eng},
  note         = {Student Paper},
  title        = {A small-scale dosimetry model of the liver tissue},
  year         = {2012},
}