Advanced

Computational patient models for simulation of dynamic gamma-camera imaging : Application to renography and peptide receptor radionuclide therapy

Brolin, Gustav LU (2017)
Abstract (Swedish)
Inom nuklearmedicinen utnyttjas radioaktiva läkemedel och strålningen som sänds ut från dessa för att diagnosticera och behandla ett flertal olika sjukdomar. Det radioaktiva läkemedlet ges ofta till patienten som en intravenös injektion, och läkemedlets egenskaper i kombination med patientens fysiologi och eventuella sjukdom avgör hur läkemedlet sedan fördelas, omsätts och utsöndras från kroppen. Denna dynamiska process kan följas med hjälp av en gammakamera (scintillationskamera) som genom att detektera strålningen från det radioaktiva ämnet skapar en bild av aktivitetsfördelningen i kroppen vid olika tidpunkter efter injektionen.
Det är i många sammanhang av intresse att använda den nuklearmedicinska bilden för att beräkna hur... (More)
Inom nuklearmedicinen utnyttjas radioaktiva läkemedel och strålningen som sänds ut från dessa för att diagnosticera och behandla ett flertal olika sjukdomar. Det radioaktiva läkemedlet ges ofta till patienten som en intravenös injektion, och läkemedlets egenskaper i kombination med patientens fysiologi och eventuella sjukdom avgör hur läkemedlet sedan fördelas, omsätts och utsöndras från kroppen. Denna dynamiska process kan följas med hjälp av en gammakamera (scintillationskamera) som genom att detektera strålningen från det radioaktiva ämnet skapar en bild av aktivitetsfördelningen i kroppen vid olika tidpunkter efter injektionen.
Det är i många sammanhang av intresse att använda den nuklearmedicinska bilden för att beräkna hur mycket av läkemedlet eller radionukliden som tagits upp i t.ex. ett organ eller tumör som funktion av tiden efter injektionen. Ett sådant sammanhang är vid renografi, en typ av njurundersökning där upptaget och utsöndringen av det radioaktiva läkemedlet avspeglar njurarnas funktion. Ett annat sådant sammanhang är vid radionuklidterapi, det vill säga behandling av cancer eller andra sjukdomar med radioaktiva läkemedel. Inom radionuklidterapi kan mätvärdena användas för att beräkna stråldoser till tumörer och friska organ. Stråldoserna avgör sedan hur mycket av det radioaktiva läkemedlet som ska ges till patienten för att maximera behandlingseffekten utan att risken för strålskador på friska organ blir oacceptabelt hög.
Det är ur ett patientsäkerhetsperspektiv givetvis av största betydelse att de mät- och beräkningsmetoder som används i dessa sammanhang ger tillförlitliga resultat, och att de mätosäkerheter och begränsningar som finns blir noggrant utredda. I detta arbete har vi undersökt tillförligheten i mätvärden som tas fram vid renografi med det radioaktiva läkemedlet 99mTc-MAG3 samt i stråldosberäkningar vid radionuklidterapi med 177Lu-DOTATATE. Detta har dels gjort med konventionella mätningar, men främst genom datorexperiment med digitala patientmodeller. Patientmodellerna har konstruerats med hjälp av befintliga datormodeller av den mänskliga anatomin i kombination med framtagna farmakokinetiska modeller, vilka beskriver hur läkemedlet fördelar sig i kroppen som funktion av tiden efter injektion. Datorsimulering av gammakamerabildtagning med dessa patientmodeller ger bilder som är mycket patientlika och har visat sig vara användbara för utredning av osäkerheter och mätnoggrannhet, vilket i förlängningen kan bidra till bättre nuklearmedicinsk diagnostik och förbättrade behandlingsresultat vid radionuklidterapi.
(Less)
Abstract
Many nuclear medicine investigations rely on gamma-camera imaging to study and quantify the distribution of radiopharmaceuticals or radionuclides in the patient as a function of time. This is typically used for diagnostic studies of physiological functions or for calculation of absorbed doses following radionuclide therapy. In this work, computational patient models (phantoms) have been developed and used for evaluation of quantitative methods and techniques relying on dynamic gamma-camera imaging.
Papers I and II concern 99mTc-MAG3 dynamic renography, a well-established diagnostic modality for evaluation of renal function. In paper I, a patient model featuring the pharmacokinetics of 99mTc-MAG3 was presented. The... (More)
Many nuclear medicine investigations rely on gamma-camera imaging to study and quantify the distribution of radiopharmaceuticals or radionuclides in the patient as a function of time. This is typically used for diagnostic studies of physiological functions or for calculation of absorbed doses following radionuclide therapy. In this work, computational patient models (phantoms) have been developed and used for evaluation of quantitative methods and techniques relying on dynamic gamma-camera imaging.
Papers I and II concern 99mTc-MAG3 dynamic renography, a well-established diagnostic modality for evaluation of renal function. In paper I, a patient model featuring the pharmacokinetics of 99mTc-MAG3 was presented. The developed framework readily allows modelling of various cases of clinical interest in a systematic manner. Dynamic image acquisition was simulated using the Monte Carlo method, and the resulting image data were encapsulated in the DICOM format to allow processing with software used in clinical practice. In paper II, this data were used to investigate the accuracy and inter-departmental variability in dynamic renography analysis, with participation from 21 nuclear medicine departments in Sweden. We found that the variability in estimates of renal TAC parameters is low and acceptable when renal function is normal, but considerably high when renal function is impaired. The accuracy of relative uptake measurements was negatively affected by the lack of attenuation correction for quantitation.
Papers III-IV concern image-based, patient-specific dosimetry in peptide receptor radionuclide therapy (PRRT) with 177Lu-DOTATATE. Paper III describes the development of computational patient models for research on image-based dosimetry, based on the same approach as used in paper I. A preliminary evaluation of a realistic dosimetry protocol, based on a single SPECT and four planar scans, was performed and it was shown that absorbed doses to organs and tumours were accurate within ±25 %. In paper IV, the patient models were used in a thorough analysis of uncertainty in renal dosimetry based entirely on SPECT/CT, and a total uncertainty of approximately 6 % (1 standard deviation) was estimated in the absorbed dose to the kidneys. In paper V, the dosimetric impact of the long-lived meta-stable isomer 177mLu was studied. Furthermore, it was investigated if current dosimetry protocols, relying on measurements limited to the first week after treatment, are sufficient to predict the long-term activity retention. The results showed a negligible contribution from 177mLu to the whole-body absorbed dose, and that measurements performed more than one week after treatment are warranted for tumour and whole-body dosimetry.
In conclusion, this thesis provides a contribution to the knowledge of measurement accuracy and uncertainty in dynamic renography and 177Lu PRRT.
(Less)
Please use this url to cite or link to this publication:
author
supervisor
opponent
  • Research Director Bardiès, Manuel, Cancer Research Center of Toulouse, France
organization
publishing date
type
Thesis
publication status
published
subject
keywords
Nuclear medicine, Gamma camera, Renography, Radionuclide therapy, Internal dosimetry, Pharmacokinetics
pages
86 pages
publisher
Lund University, Faculty of Science, Department of Medical Radiation Physics
defense location
Lecture hall F3, Skåne University Hospital, Lund
defense date
2017-10-06 09:00
ISBN
978-91-7753-386-3
978-91-7753-385-6
language
English
LU publication?
yes
id
30433da3-37b7-493a-a310-14c6f7ca1b22
date added to LUP
2017-09-12 11:00:19
date last changed
2017-09-15 14:22:21
@phdthesis{30433da3-37b7-493a-a310-14c6f7ca1b22,
  abstract     = {Many nuclear medicine investigations rely on gamma-camera imaging to study and quantify the distribution of radiopharmaceuticals or radionuclides in the patient as a function of time. This is typically used for diagnostic studies of physiological functions or for calculation of absorbed doses following radionuclide therapy. In this work, computational patient models (phantoms) have been developed and used for evaluation of quantitative methods and techniques relying on dynamic gamma-camera imaging.<br/>Papers I and II concern <sup>99m</sup>Tc-MAG3 dynamic renography, a well-established diagnostic modality for evaluation of renal function. In paper I, a patient model featuring the pharmacokinetics of <sup>99m</sup>Tc-MAG3 was presented. The developed framework readily allows modelling of various cases of clinical interest in a systematic manner. Dynamic image acquisition was simulated using the Monte Carlo method, and the resulting image data were encapsulated in the DICOM format to allow processing with software used in clinical practice. In paper II, this data were used to investigate the accuracy and inter-departmental variability in dynamic renography analysis, with participation from 21 nuclear medicine departments in Sweden. We found that the variability in estimates of renal TAC parameters is low and acceptable when renal function is normal, but considerably high when renal function is impaired. The accuracy of relative uptake measurements was negatively affected by the lack of attenuation correction for quantitation. <br/>Papers III-IV concern image-based, patient-specific dosimetry in peptide receptor radionuclide therapy (PRRT) with <sup>177</sup>Lu-DOTATATE. Paper III describes the development of computational patient models for research on image-based dosimetry, based on the same approach as used in paper I. A preliminary evaluation of a realistic dosimetry protocol, based on a single SPECT and four planar scans, was performed and it was shown that absorbed doses to organs and tumours were accurate within ±25 %. In paper IV, the patient models were used in a thorough analysis of uncertainty in renal dosimetry based entirely on SPECT/CT, and a total uncertainty of approximately 6 % (1 standard deviation) was estimated in the absorbed dose to the kidneys. In paper V, the dosimetric impact of the long-lived meta-stable isomer <sup>177m</sup>Lu was studied. Furthermore, it was investigated if current dosimetry protocols, relying on measurements limited to the first week after treatment, are sufficient to predict the long-term activity retention. The results showed a negligible contribution from <sup>177m</sup>Lu to the whole-body absorbed dose, and that measurements performed more than one week after treatment are warranted for tumour and whole-body dosimetry. <br/>In conclusion, this thesis provides a contribution to the knowledge of measurement accuracy and uncertainty in dynamic renography and <sup>177</sup>Lu PRRT.<br/>},
  author       = {Brolin, Gustav},
  isbn         = {978-91-7753-386-3},
  keyword      = {Nuclear medicine, Gamma camera,Renography, Radionuclide therapy, Internal dosimetry,Pharmacokinetics},
  language     = {eng},
  pages        = {86},
  publisher    = {Lund University, Faculty of Science, Department of Medical Radiation Physics},
  school       = {Lund University},
  title        = {Computational patient models for simulation of dynamic gamma-camera imaging : Application to renography and peptide receptor radionuclide therapy},
  year         = {2017},
}