PET for bone imaging

Positron emission tomography for Bone Imaging, as an in vivo tracer technique, allows the measurement of the regional concentration of radioactivity proportional to the image pixel values averaged over a region of interest (ROI) in bones. Positron emission tomography is a functional imaging technique that uses [18F]NaF radiotracer to visualise and quantify regional bone metabolism and blood flow. [18F]NaF has been used for imaging bones for the last 60 years. This article focuses on the pharmacokinetics of [18F]NaF in bones, and various semi-quantitative and quantitative methods for quantifying regional bone metabolism using [18F]NaF PET images.

Why [18F]NaF PET?

The measurement of regional bone metabolism is critical to understand the pathophysiology of metabolic bone diseases.

  • Bone biopsy is considered the gold standard to quantify bone turnover; however, it is invasive, complex and costly to perform and subject to significant measurement errors.[1]
  • Measurements of serum or urine biomarkers of bone turnover are simple, cheap, quick, and non-invasive in measuring changes in bone metabolism, but only provide information on the global skeleton.[2]
  • The functional imaging technique of dynamic [18F]NaF PET scans can quantify regional bone turnover at specific sites of clinical importance such as the lumbar spine and hip[3] and has been validated by comparison with the gold standard of bone biopsy.[4][5][6]

Pharmacokinetics of [18F]NaF

The chemically stable anion of Fluorine-18-Fluoride is a bone-seeking radiotracer in skeletal imaging. [18F]NaF has an affinity to deposit at areas where the bone is newly mineralizing.[5][7][8][9][10] Many studies have [18F]NaF PET to measure bone metabolism at the hip,[3] lumbar spine, and humerus.[11] [18F]NaF is taken-up in an exponential manner representing the equilibration of tracer with the extracellular and cellular fluid spaces with a half-life of 0.4 hours, and with kidneys with a half-life of 2.4 hours.[12] The single passage extraction of [18F]NaF in bone is 100%.[13] After an hour, only 10% of the injected activity remains in the blood.[14]

18F- ions are considered to occupy extracellular fluid spaces because, firstly, they equilibrate with transcellular fluid spaces and secondly, they are not entirely extracellular ions.[15][16][17] Fluoride undergoes equilibrium with hydrogen fluoride, which has a high permeability allowing fluoride to cross the plasma blood membrane.[18] The fluoride circulation in red blood cells accounts for 30%.[19] However, it is freely available to the bone surface for uptake because the equilibrium between erythrocytes and plasma is much faster than the capillary transit time. This is supported by studies reporting 100% single-passage extraction of whole-blood 18F- ion by bone[13] and the rapid release of 18F- ions from erythrocytes with a rate constant of 0.3 per second.[20]

[18F]NaF is also taken-up by immature erythrocytes in the bone marrow,[21] which plays a role in fluoride kinetics.[22] The plasma protein binding of [18F]NaF is negligible.[23] [18F]NaF renal clearance is affected by diet[24] and pH level,[25] due to its re-absorption in the nephron, which is mediated by hydrogen fluoride.[26] However, large differences in urine flow rate[19] are avoided for controlled experiments by keeping patents well hydrated.[21]

The exchangeable pool and the size of the metabolically active surfaces in bones determines the amount of tracer accumulated or exchanged[27] with bone extracellular fluid,[28] chemisorption onto hydroxyapatite crystals to form fluorapatite,[14][29][9] as shown in Equation-1:[30][31]

Equation-1

Fluoride ions from the crystalline matrix of bone are released when the bone is remodelled, thus providing a measure of the rate of bone metabolism.[32][33][34]

Measuring SUV

Definition
The two image in the top row (the image on the left hand side is plotted on log scale and on the right hand side is plotted on linear scale) show the output of the spectral analysis showing its frequencies components grouped around three clusters, referred to as high, intermediate and low frequencies, supporting the assumption of three compartments in the Hawkins model corresponding to plasma, bone ECF and bone mineral compartment respectively. The image at the bottom row shows the IRF plotted using the frequency components obtained previously.

The standardized uptake value (SUV) is defined as tissue concentration (KBq/ml) divided by activity injected normalized for body weight.[35]

Appropriateness

The SUV measured from the large ROI smooths out the noise and, therefore, more appropriate in [18F]NaF bone studies as the radiotracer is fairly uniformly taken up throughout the bone. The measurement of SUV is easy,[36] cheap, and quicker to perform, making it more attractive for clinical use. It has been used in diagnosing and assessing the efficacy of therapy.[37][38] SUV can be measured at a single site, or the whole skeleton using a series of static scans and restricted by the small field-of-view of the PET scanner.[32]

Known Issues

The SUV has emerged as a clinically useful, albeit controversial, semi-quantitative tool in PET analysis.[39] Standardizing imaging protocols and measuring the SUV at the same time post-injection of the radiotracer, is necessary to obtain a correct SUV[40] because imaging before the uptake plateau introduces unpredictable errors of up to 50% with SUVs.[41] Noise, image resolution, and reconstruction do affect the accuracy of SUVs, but correction with phantom can minimize these differences when comparing SUVs for multi-centre clinical trials.[42][43] SUV may lack sensitivity in measuring response to treatment as it is a simple measure of tracer uptake in bone, which is affected by the tracer uptake in other competing tissues and organs in addition to the target ROI.[44][45]

Measuring Ki

The quantification of dynamic PET studies to measure Ki requires the measurement of the skeletal time-activity curves (TAC) from the region of interest (ROI) and the arterial input function (AIF), which can be measured in various different ways. However, the most common is to correct the image-based blood time-activity curves using several venous blood samples taken at discrete time points while the patient is scanned. The calculation of rate constants or Ki requires three steps:[3]

  • Measurement of the arterial input function (AIF), which acts as the first input to the mathematical model of tracer distribution.
  • Measurement of the time-activity curve (TAC) within the skeletal region of interest, which acts as the second input to the mathematical model of tracer distribution.
  • Kinetic modelling of AIF and TAC using mathematical modelling to obtain net plasma clearance (Ki) to the bone mineral.
A bone TAC is modelled as a convolution of measured arterial input function with IRF. The estimates for IRF are obtained iteratively to minimise the differences between the bone curve and the convolution of estimated IRF with input function curve. The curve in green shows the initial estimates of the IRF and the blue curve is the final IRF which minimises the differences between the estimated bone curve and the true bone curve. Ki is obtained from the intercept of the linear fit to the slow component of this exponential curve which is considered the plasma clearance to the bone mineral, i.e. were the red line cuts the y axis.

Spectral method

The method was first described by Cunningham & Jones[46] in 1993 for the analysis of dynamic PET data obtained in the brain. It assumes that the tissue impulse response function (IRF) can be described as a combination of many exponentials. Since A tissue TAC can be expressed as a convolution of measured arterial input function with IRF, Cbone(t) can be expressed as:

where, is a convolution operator, Cbone(t) is the bone tissue activity concentration of tracer (in units: MBq/ml) over a period of time t, Cplasma(t) is the plasma concentration of tracer (in units: MBq/ml) over a period of time t, IRF(t) is equal to the sum of exponentials, β values are fixed between 0.0001 sec−1 and 0.1 sec−1 in intervals of 0.0001, n is the number of α components that resulted from the analysis and β1, β2,…, βn corresponds to the respective α1, α2,…, αn components from the resulted spectrum. The values of α are then estimated from the analysis by fitting multi-exponential to the IRF. The intercept of the linear fit to the slow component of this exponential curve is considered the plasma clearance (Ki) to the bone mineral.

Deconvolution method

The method was first described by Williams et al. in the clinical context.[47] The method was used by numerous other studies.[48][49][50] This is perhaps the simplest of all the mathematical methods for the calculation of Ki but the one most sensitive to noise present in the data. A tissue TAC is modelled as a convolution of measured arterial input function with IRF, the estimates for IRF are obtained iteratively to minimise the differences between the left- and right-hand side of the following Equation:

where, is a convolution operator, Cbone(t) is the bone tissue activity concentration of tracer (in units: MBq/ml) over a period of time t, Cplasma(t) is the plasma concentration of tracer (in units: MBq/ml) over a period of time t, and IRF(t) is the impulse response of the system (i.e., a tissue in this case). The Ki is obtained from the IRF in a similar fashion to that obtained for the spectral analysis, as shown in the figure.

Hawkins model
A diagrammatic view of the process of kinetic modelling using Hawkins model used to calculate the rate of bone metabolism at a skeletal site. Cp refers to the plasma concentration of the tracer, Ce refers to the tracer concentration in ECF compartment, Cb refers to the concentration of tracer in bone mineral compartment, M1 refers to mass of tracer in the Ce compartment, M2 refers to the mass of tracer in the Cb compartment, CT is the total mass in the Ce+Cb, PVE refers to the partial volume correction, FA refers to the femoral artery, ROI refers to region of the interest, B-Exp refers to the bi-exponential, .

The measurement of Ki from dynamic PET scans require tracer kinetic modelling to obtain the model parameters describing the biological processes in bone, as described by Hawkins et al.[22] Since this model has two tissue compartments, it is sometimes called a two-tissue compartmental model. Various different versions of this model exist; however, the most fundamental approach is considered here with two tissue compartments and four tracer-exchange parameters. The whole kinetic modelling process using Hawkins model can be summed up in a single image as seen on the right-hand-side. The following differential equations are solved to obtain the rate constants:

The rate constant K1 (in units: ml/min/ml) describes the unidirectional clearance of fluoride from plasma to the whole of the bone tissue, k2 (in units: min−1) describes the reverse transport of fluoride from the ECF compartment to plasma, k3 and k4 (in units min−1) describe the forward and backward transportation of fluoride from the bone mineral compartment.

Ki represents the net plasma clearance to bone mineral only. Ki is a function of both K1, reflecting bone blood flow, and the fraction of the tracer that undergoes specific binding to the bone mineral k3 / (k2 + k3). Therefore,

Hawkins et al. found that the inclusion of an additional parameter called fractional blood volume (BV), representing the vascular tissue spaces within the ROI, improved the data fitting problem, although this improvement was not statistically significant.[51]

Patlak method

Patlak method[52] is based on the assumption that the backflow of tracer from bone mineral to bone ECF is zero (i.e., k4=0). The calculation of Ki using Patlak method is simpler than using non-linear regression (NLR) fitting the arterial input function and the tissue time-activity curve data to the Hawkins model. It is crucial to note that Patlak method can only measure bone plasma clearance (Ki), and cannot measure the individual kinetic parameters, K1, k2, k3, or k4.

The concentration of tracer in tissue region-of-interest can be represented as a sum of concentration in bone ECF and the bone mineral. It can be mathematically represented as

where, within the tissue region-of-interest from the PET image, Cbone(T) is the bone tissue activity concentration of tracer (in units: MBq/ml) at any time T, Cplasma(T) is the plasma concentration of tracer (in units: MBq/ml) at time T, Vo is the fraction of the ROI occupied by the ECF compartment, and is the area under the plasma curve is the net tracer delivery to the tissue region of interest (in units: MBq.Sec/ml) over time T. The Patlak equation is a linear equation of the form

Patlak analysis where a linear regression is fitted between the data on y- and x-axis to obtain the estimates of the Ki, which is the slope of the fitted regression line.

Therefore, linear regression is fitted to the data plotted on Y- and X-axis between 4–60 minutes to obtain m and c values, where m is the slope of the regression line representing Ki and c is the Y-intercept of the regression line representing Vo.[52]

Siddique-Blake method

The calculation of Ki using arterial input function, time-activity curve, and Hawkins model was limited to a small skeletal region covered by the narrow field-of-view of the PET scanner while acquiring a dynamic scan. However, Siddique et al.[53] showed in 2012 that it is possible to measure Ki values in bones using static [18F]NaF PET scans. Blake et al.[32] later showed in 2019 that the Ki obtained using the Siddique-Blake method has precision errors of less than 10%. The Siddique-Blake approach is based on the combination of the Patlak method,[52] the semi-population based arterial input function,[54] and the information that Vo does not significantly change post-treatment. This method uses the information that a linear regression line can be plotted using the data from a minimum of two time-points, to obtain m and c as explained in the Patlak method. However, if Vo is known or fixed, only one single static PET image is required to obtain the second time-point to measure m, representing the Ki value. This method should be applied with great caution to other clinical areas where these assumptions may not hold true.

SUV vs Ki

The most fundamental difference between SUV and Ki values is that SUV is a simple measure of uptake, which is normalized to body weight and injected activity. The SUV does not take into consideration the tracer delivery to the local region of interest from where the measurements are obtained, therefore, affected by the physiological process consuming [18F]NaF elsewhere in the body. On the other hand, Ki measures the plasma clearance to bone mineral, taking into account the tracer uptake elsewhere in the body affecting the delivery of tracer to the region of interest from where the measurements are obtained. The difference in the measurement of Ki and SUV in bone tissue using [18F]NaF are explained in more detail by Blake et al.[34]

It is critical to note that most of the methods for calculating Ki require dynamic PET scanning over an hour, except, the Siddique-Blake methods. Dynamic scanning is complicated and costly. However, the calculation of SUV requires a single static PET scan performed approximately 45–60 minutes post-tracer injection at any region imaged within the skeleton.

Many researchers have shown a high correlation between SUV and Ki values at various skeletal sites.[55][56][57] However, SUV and Ki methods can contradict for measuring response to treatment.[45] Since SUV has not been validated against the histomorphometry, its usefulness in bone studies measuring response to treatment and disease progression is uncertain.

See also

References
  1. Compston, J.E.; Croucher, P.I. (August 1991). "Histomorphometric assessment of trabecular bone remodelling in osteoporosis". Bone and Mineral. 14 (2): 91–102. doi:10.1016/0169-6009(91)90086-f. ISSN 0169-6009. PMID 1912765.
  2. Beck Jensen, J. E.; Kollerup, G.; Ørensen, H. A.; Nielsen, S. Pors; Sørensen, O. H. (January 1997). "A single measurement of biochemical markers of bone turnover has limited utility in the individual person". Scandinavian Journal of Clinical and Laboratory Investigation. 57 (4): 351–359. doi:10.3109/00365519709099408. ISSN 0036-5513. PMID 9249882.
  3. Puri, T.; Frost, M. L.; Curran, K. M.; Siddique, M.; Moore, A. E. B.; Cook, G. J. R.; Marsden, P. K.; Fogelman, I.; Blake, G. M. (2012-05-12). "Differences in regional bone metabolism at the spine and hip: a quantitative study using 18F-fluoride positron emission tomography". Osteoporosis International. 24 (2): 633–639. doi:10.1007/s00198-012-2006-x. ISSN 0937-941X. PMID 22581294. S2CID 22146999.
  4. Aaltonen, Louise; Koivuviita, Niina; Seppänen, Marko; Tong, Xiaoyu; Kröger, Heikki; Löyttyniemi, Eliisa; Metsärinne, Kaj (May 2020). "Correlation between 18F-Sodium Fluoride positron emission tomography and bone histomorphometry in dialysis patients". Bone. 134: 115267. doi:10.1016/j.bone.2020.115267. ISSN 8756-3282. PMID 32058018.
  5. Messa, C. (1993-10-01). "Bone metabolic activity measured with positron emission tomography and [18F]fluoride ion in renal osteodystrophy: correlation with bone histomorphometry". Journal of Clinical Endocrinology & Metabolism. 77 (4): 949–955. doi:10.1210/jc.77.4.949. ISSN 0021-972X. PMID 8408470.
  6. Piert, Morand; Zittel, Tilman T.; Machulla, Hans-Jurgen; Becker, Georg Alexander; Jahn, Michael; Maier, Gerhard; Bares, Roland; Becker, Horst Dieter (1998-08-01). "Blood Flow Measurements with [15O]H2O and [18F]Fluoride Ion PET in Porcine Vertebrae". Journal of Bone and Mineral Research. 13 (8): 1328–1336. doi:10.1359/jbmr.1998.13.8.1328. ISSN 0884-0431. PMID 9718202. S2CID 19824951.
  7. Piert, Morand; Machulla, Hans-Jürgen; Jahn, Michael; Stahlschmidt, Anke; Becker, Georg A.; Zittel, Tilman T. (2002-04-13). "Coupling of porcine bone blood flow and metabolism in high-turnover bone disease measured by [15O]H2O and [18F]fluoride ion positron emission tomography". European Journal of Nuclear Medicine and Molecular Imaging. 29 (7): 907–914. doi:10.1007/s00259-002-0797-2. ISSN 1619-7070. PMID 12111131. S2CID 2591493.
  8. Schumichen, C.; Rempfle, H.; Wagner, M.; Hoffmann, G. (1979). "The short-term fixation of radiopharmaceuticals in bone". European Journal of Nuclear Medicine. 4 (6): 423–428. doi:10.1007/bf00300839. ISSN 0340-6997. PMID 520356. S2CID 23813593.
  9. Narita, Naoki; Kato, Kazuo; Nakagaki, Haruo; Ohno, Norikazu; Kameyama, Yoichiro; Weatherell, John A. (March 1990). "Distribution of fluoride concentration in the rat's bone". Calcified Tissue International. 46 (3): 200–204. doi:10.1007/bf02555045. ISSN 0171-967X. PMID 2106380. S2CID 2707183.
  10. REEVE, J.; ARLOT, M.; WOOTTON, R.; EDOUARD, C.; TELLEZ, M.; HESP, R.; GREEN, J. R.; MEUNIER, P. J. (June 1988). "Skeletal Blood Flow, Iliac Histomorphometry, and Strontium Kinetics in Osteoporosis: A Relationship Between Blood Flow and Corrected Apposition Rate". The Journal of Clinical Endocrinology & Metabolism. 66 (6): 1124–1131. doi:10.1210/jcem-66-6-1124. ISSN 0021-972X. PMID 3372678.
  11. Cook, Gary J. R.; Lodge, Martin A.; Blake, Glen M.; Marsden, Paul K.; Fogelman, Ignac (2010-02-18). "Differences in Skeletal Kinetics Between Vertebral and Humeral Bone Measured by 18F-Fluoride Positron Emission Tomography in Postmenopausal Women". Journal of Bone and Mineral Research. 15 (4): 763–769. doi:10.1359/jbmr.2000.15.4.763. ISSN 0884-0431. PMID 10780868. S2CID 10630967.
  12. Krishnamurthy, GT; Huebotter, RJ; Tubis, M; Blahd, WH (February 1976). "Pharmaco-kinetics of current skeletal-seeking radiopharmaceuticals". American Journal of Roentgenology. 126 (2): 293–301. doi:10.2214/ajr.126.2.293. ISSN 0361-803X. PMID 175699.
  13. Wootton, R; Dore, C (November 1986). "The single-passage extraction of 18 F in rabbit bone". Clinical Physics and Physiological Measurement. 7 (4): 333–343. Bibcode:1986CPPM....7..333W. doi:10.1088/0143-0815/7/4/003. ISSN 0143-0815. PMID 3791879.
  14. Blau, Monte; Ganatra, Ramanik; Bender, Merrill A. (January 1972). "18F-fluoride for bone imaging". Seminars in Nuclear Medicine. 2 (1): 31–37. doi:10.1016/s0001-2998(72)80005-9. ISSN 0001-2998. PMID 5059349.
  15. Edelman, I.S.; Leibman, J. (August 1959). "Anatomy of body water and electrolytes". The American Journal of Medicine. 27 (2): 256–277. doi:10.1016/0002-9343(59)90346-8. ISSN 0002-9343. PMID 13819266.
  16. Pierson, R. N.; Price, D. C.; Wang, J.; Jain, R. K. (1978-09-01). "Extracellular water measurements: organ tracer kinetics of bromide and sucrose in rats and man". American Journal of Physiology. Renal Physiology. 235 (3): F254–F264. doi:10.1152/ajprenal.1978.235.3.f254. ISSN 1931-857X. PMID 696835.
  17. Staffurth, J. S.; Birchall, I. (January 1959). "The Significance of the Protein Bound Radioactive Iodine Determination in Hyperthyroidism". Acta Endocrinologica. 30 (1): 42–52. doi:10.1530/acta.0.0300042. ISSN 0804-4643. PMID 13605561.
  18. Whitford, G.M. (June 1994). "Intake and Metabolism of Fluoride". Advances in Dental Research. 8 (1): 5–14. doi:10.1177/08959374940080011001. ISSN 0895-9374. PMID 7993560. S2CID 21763028.
  19. Hosking, D. J.; Chamberlain, M. J. (1972-02-01). "Studies in Man with 18F". Clinical Science. 42 (2): 153–161. doi:10.1042/cs0420153. ISSN 0009-9287. PMID 5058570.
  20. TOSTESON, D. C. (January 1959). "Halide Transport in Red Blood Cells". Acta Physiologica Scandinavica. 46 (1): 19–41. doi:10.1111/j.1748-1716.1959.tb01734.x. ISSN 0001-6772.
  21. Blake, Glen M.; Park-Holohan, So-Jin; Cook, Gary J.R.; Fogelman, Ignac (January 2001). "Quantitative studies of bone with the use of 18F-fluoride and 99mTc-methylene diphosphonate". Seminars in Nuclear Medicine. 31 (1): 28–49. doi:10.1053/snuc.2001.18742. ISSN 0001-2998. PMID 11200203.
  22. Hoh, Carl K.; Hawkins, Randall A.; Dahlbom, Magnus; Glaspy, John A.; Seeger, Leanne L.; Choi, Yong; Schiepers, Christiaan W.; Huang, Sung-cheng; Satyamurthy, Nagichettiar; Barrio, Jorge R.; Phelps, Michael E. (January 1993). "Whole Body Skeletal Imaging with [18F]Fluoride Ion and PET". Journal of Computer Assisted Tomography. 17 (1): 34–41. doi:10.1097/00004728-199301000-00005. ISSN 0363-8715. PMID 8419436.
  23. TAVES, DONALD R. (November 1968). "Electrophoretic Mobility of Serum Fluoride". Nature. 220 (5167): 582–583. Bibcode:1968Natur.220..582T. doi:10.1038/220582a0. ISSN 0028-0836. PMID 5686731. S2CID 4220484.
  24. Ekstrand, J.; Spak, C. J.; Ehrnebo, M. (2009-03-13). "Renal Clearance of Fluoride in a Steady State Condition in Man: Influence of Urinary Flow and pH Changes by Diet". Acta Pharmacologica et Toxicologica. 50 (5): 321–325. doi:10.1111/j.1600-0773.1982.tb00982.x. ISSN 0001-6683. PMID 7113707.
  25. Ekstrand, Jan; Ehrnebo, Mats; Boréus, Lars O. (March 1978). "Fluoride bioavailability after intravenous and oral administration: Importance of renal clearance and urine flow". Clinical Pharmacology & Therapeutics. 23 (3): 329–337. doi:10.1002/cpt1978233329. ISSN 0009-9236. PMID 627140. S2CID 26176903.
  26. Whitford, GM; Pashley, DH; Stringer, GI (1976-02-01). "Fluoride renal clearance: a pH-dependent event". American Journal of Physiology. Legacy Content. 230 (2): 527–532. doi:10.1152/ajplegacy.1976.230.2.527. ISSN 0002-9513. PMID 1259032.
  27. Costeas, A.; Woodard, H. Q.; Laughlin, J. S. (May 1971). "Comparative Kinetics of Calcium and Fluoride in Rabbit Bone". Radiation Research. 46 (2): 317. Bibcode:1971RadR...46..317C. doi:10.2307/3573023. ISSN 0033-7587. JSTOR 3573023. PMID 5564840.
  28. Walker, P. G. (November 1958). "THE CHEMICAL DYNAMICS OF BONE MINERAL. By William F. Neuman and Margaret W. Neuman. 9¼x5½ in. Pp. xi+209, with 51 figures and 24 tables. Index. 1958. Chicago: The University of Chicago Press. London: Cambridge University Press. Price 37s. 6d". The Journal of Bone and Joint Surgery. British Volume. 40-B (4): 846. doi:10.1302/0301-620x.40b4.846. ISSN 0301-620X.
  29. Ishiguro, Koji; Nakagaki, Haruo; Tsuboi, Shinji; Narita, Naoki; Kato, Kazuo; Li, Jianxue; Kamei, Hideo; Yoshioka, Ikuo; Miyauchi, Kenichi; Hosoe, Hiroyo; Shimano, Ryouyu (April 1993). "Distribution of fluoride in cortical bone of human rib". Calcified Tissue International. 52 (4): 278–282. doi:10.1007/bf00296652. ISSN 0171-967X. PMID 8467408. S2CID 31137242.
  30. Grynpas, Marc D. (2010-02-25). "Fluoride effects on bone crystals". Journal of Bone and Mineral Research. 5 (S1): S169–S175. doi:10.1002/jbmr.5650051362. ISSN 0884-0431. PMID 2187325. S2CID 22713623.
  31. Jones, Alun G.; Francis, Marion D.; Davis, Michael A. (January 1976). "Bone scanning: Radionuclidic reaction mechanisms". Seminars in Nuclear Medicine. 6 (1): 3–18. doi:10.1016/s0001-2998(76)80032-3. ISSN 0001-2998. PMID 174228.
  32. Blake, Glen M.; Puri, Tanuj; Siddique, Musib; Frost, Michelle L.; Moore, Amelia E. B.; Fogelman, Ignac (February 2018). "Site specific measurements of bone formation using [18F] sodium fluoride PET/CT". Quantitative Imaging in Medicine and Surgery. 8 (1): 47–59. doi:10.21037/qims.2018.01.02. PMC 5835654. PMID 29541623.
  33. Grant, F. D.; Fahey, F. H.; Packard, A. B.; Davis, R. T.; Alavi, A.; Treves, S. T. (2007-12-12). "Skeletal PET with 18F-Fluoride: Applying New Technology to an Old Tracer". Journal of Nuclear Medicine. 49 (1): 68–78. doi:10.2967/jnumed.106.037200. ISSN 0161-5505. PMID 18077529.
  34. Blake, Glen M.; Siddique, Musib; Frost, Michelle L.; Moore, Amelia E.B.; Fogelman, Ignac (September 2011). "Radionuclide studies of bone metabolism: Do bone uptake and bone plasma clearance provide equivalent measurements of bone turnover?". Bone. 49 (3): 537–542. doi:10.1016/j.bone.2011.05.031. ISSN 8756-3282. PMID 21689803.
  35. Huang, (Henry) Sung-Cheng (October 2000). "Anatomy of SUV". Nuclear Medicine and Biology. 27 (7): 643–646. doi:10.1016/s0969-8051(00)00155-4. ISSN 0969-8051. PMID 11091106.
  36. Basu, Sandip; Zaidi, Habib; Houseni, Mohamed; Bural, Gonca; Udupa, Jay; Acton, Paul; Torigian, Drew A.; Alavi, Abass (May 2007). "Novel Quantitative Techniques for Assessing Regional and Global Function and Structure Based on Modern Imaging Modalities: Implications for Normal Variation, Aging and Diseased States". Seminars in Nuclear Medicine. 37 (3): 223–239. doi:10.1053/j.semnuclmed.2007.01.005. ISSN 0001-2998. PMID 17418154.
  37. Lucignani, G.; Paganelli, G.; Bombardieri, E. (July 2004). "The use of standardized uptake values for assessing FDG uptake with PET in oncology: a clinical perspective". Nuclear Medicine Communications. 25 (7): 651–656. doi:10.1097/01.mnm.0000134329.30912.49. ISSN 0143-3636. PMID 15208491. S2CID 38728335.
  38. Frost, M. L.; Blake, G. M.; Park-Holohan, S.-J.; Cook, G. J.R.; Curran, K. M.; Marsden, P. K.; Fogelman, I. (2008-04-15). "Long-Term Precision of 18F-Fluoride PET Skeletal Kinetic Studies in the Assessment of Bone Metabolism". Journal of Nuclear Medicine. 49 (5): 700–707. doi:10.2967/jnumed.107.046987. ISSN 0161-5505. PMID 18413385.
  39. Visser, E. P.; Boerman, O. C.; Oyen, W. J.G. (2010-01-15). "SUV: From Silly Useless Value to Smart Uptake Value". Journal of Nuclear Medicine. 51 (2): 173–175. doi:10.2967/jnumed.109.068411. ISSN 0161-5505. PMID 20080897.
  40. Halama, J; Sadjak, R; Wagner, R (June 2006). "SU-FF-I-82: Variability and Accuracy of Standardized Uptake Values in FDG PET Scans". Medical Physics. 33 (6Part4): 2015–2016. Bibcode:2006MedPh..33.2015H. doi:10.1118/1.2240762. ISSN 0094-2405.
  41. Fischman, Alan J.; Alpert, Nathaniel M.; Babich, John W.; Rubin, Robert H. (January 1997). "The Role of Positron Emission Tomography in Pharmacokinetic Analysis". Drug Metabolism Reviews. 29 (4): 923–956. doi:10.3109/03602539709002238. ISSN 0360-2532. PMID 9421680.
  42. Krak, Nanda C.; Boellaard, R.; Hoekstra, Otto S.; Twisk, Jos W. R.; Hoekstra, Corneline J.; Lammertsma, Adriaan A. (2004-10-15). "Effects of ROI definition and reconstruction method on quantitative outcome and applicability in a response monitoring trial". European Journal of Nuclear Medicine and Molecular Imaging. 32 (3): 294–301. doi:10.1007/s00259-004-1566-1. ISSN 1619-7070. PMID 15791438. S2CID 22518269.
  43. Westerterp, Marinke; Pruim, Jan; Oyen, Wim; Hoekstra, Otto; Paans, Anne; Visser, Eric; van Lanschot, Jan; Sloof, Gerrit; Boellaard, Ronald (2006-10-11). "Quantification of FDG PET studies using standardised uptake values in multi-centre trials: effects of image reconstruction, resolution and ROI definition parameters". European Journal of Nuclear Medicine and Molecular Imaging. 34 (3): 392–404. doi:10.1007/s00259-006-0224-1. ISSN 1619-7070. PMID 17033848. S2CID 1521701.
  44. Blake, G. M.; Frost, M. L.; Fogelman, I. (2009-10-16). "Quantitative Radionuclide Studies of Bone". Journal of Nuclear Medicine. 50 (11): 1747–1750. doi:10.2967/jnumed.109.063263. ISSN 0161-5505. PMID 19837752.
  45. Frost, Michelle L; Siddique, Musib; Blake, Glen M; Moore, Amelia EB; Schleyer, Paul J; Dunn, Joel T; Somer, Edward J; Marsden, Paul K; Eastell, Richard; Fogelman, Ignac (May 2011). "Differential effects of teriparatide on regional bone formation using 18F-fluoride positron emission tomography". Journal of Bone and Mineral Research. 26 (5): 1002–1011. doi:10.1002/jbmr.305. ISSN 0884-0431. PMID 21542003. S2CID 40840920.
  46. Cunningham, Vincent J.; Jones, Terry (January 1993). "Spectral Analysis of Dynamic PET Studies". Journal of Cerebral Blood Flow & Metabolism. 13 (1): 15–23. doi:10.1038/jcbfm.1993.5. ISSN 0271-678X. PMID 8417003.
  47. Spedding, V. (2001). "Live laboratory will analyse real-time market data". Quantitative Finance. 1 (6): 568–570. doi:10.1088/1469-7688/1/6/606. ISSN 1469-7688. S2CID 154537213.
  48. Liberati, D.; Turkheimer, F. (1999). "Linear spectral deconvolution of catabolic plasma concentration decay in dialysis". Medical & Biological Engineering & Computing. 37 (3): 391–395. doi:10.1007/bf02513317. ISSN 0140-0118. PMID 10505392. S2CID 25080033.
  49. Lau, Chi-hoi Lun, Pak-kong Daniel Feng, D. David (1998). Non-invasive quantification of physiological processes with dynamic PET using blind deconvolution. IEEE. OCLC 697321031.CS1 maint: multiple names: authors list (link)
  50. Chi-Hoi Lau; Lun, D.P.-K.; Dagan Feng (1998). "Non-invasive quantification of physiological processes with dynamic PET using blind deconvolution". Proceedings of the 1998 IEEE International Conference on Acoustics, Speech and Signal Processing, ICASSP '98 (Cat. No.98CH36181). IEEE. 3: 1805–1808. doi:10.1109/icassp.1998.681811. ISBN 0-7803-4428-6. S2CID 5947145.
  51. Puri, Tanuj; Blake, Glen M.; Frost, Michelle L.; Siddique, Musib; Moore, Amelia E.B.; Marsden, Paul K.; Cook, Gary J.R.; Fogelman, Ignac; Curran, Kathleen M. (June 2012). "Comparison of six quantitative methods for the measurement of bone turnover at the hip and lumbar spine using 18F-fluoride PET-CT". Nuclear Medicine Communications. 33 (6): 597–606. doi:10.1097/MNM.0b013e3283512adb. ISSN 0143-3636. PMID 22441132. S2CID 23490366.
  52. Patlak, Clifford S.; Blasberg, Ronald G.; Fenstermacher, Joseph D. (March 1983). "Graphical Evaluation of Blood-to-Brain Transfer Constants from Multiple-Time Uptake Data". Journal of Cerebral Blood Flow & Metabolism. 3 (1): 1–7. doi:10.1038/jcbfm.1983.1. ISSN 0271-678X. PMID 6822610.
  53. Siddique, Musib; Blake, Glen M.; Frost, Michelle L.; Moore, Amelia E. B.; Puri, Tanuj; Marsden, Paul K.; Fogelman, Ignac (2011-11-08). "Estimation of regional bone metabolism from whole-body 18F-fluoride PET static images". European Journal of Nuclear Medicine and Molecular Imaging. 39 (2): 337–343. doi:10.1007/s00259-011-1966-y. ISSN 1619-7070. PMID 22065012. S2CID 23959977.
  54. Blake, Glen Mervyn; Siddique, Musib; Puri, Tanuj; Frost, Michelle Lorraine; Moore, Amelia Elizabeth; Cook, Gary James R.; Fogelman, Ignac (August 2012). "A semipopulation input function for quantifying static and dynamic 18F-fluoride PET scans". Nuclear Medicine Communications. 33 (8): 881–888. doi:10.1097/mnm.0b013e3283550275. ISSN 0143-3636. PMID 22617486. S2CID 42973690.
  55. Puri, Tanuj; Blake, Glen M.; Frost, Michelle L.; Siddique, Musib; Moore, Amelia E.B.; Marsden, Paul K.; Cook, Gary J.R.; Fogelman, Ignac; Curran, Kathleen M. (June 2012). "Comparison of six quantitative methods for the measurement of bone turnover at the hip and lumbar spine using 18F-fluoride PET-CT". Nuclear Medicine Communications. 33 (6): 597–606. doi:10.1097/mnm.0b013e3283512adb. ISSN 0143-3636. PMID 22441132. S2CID 23490366.
  56. BRENNER, W. (2004). "Comparison of different quantitative approaches to 18F-fluoride PET scans". J Nucl Med. 45 (9): 1493–500. PMID 15347716.
  57. Brenner, Winfried; Vernon, Cheryl; Conrad, ErnestU.; Eary, JanetF. (2004-06-10). "Assessment of the metabolic activity of bone grafts with 18F-fluoride PET". European Journal of Nuclear Medicine and Molecular Imaging. 31 (9): 1291–8. doi:10.1007/s00259-004-1568-z. ISSN 1619-7070. PMID 15197502. S2CID 10000344.
Library resources about
PET
This article is issued from Wikipedia. The text is licensed under Creative Commons - Attribution - Sharealike. Additional terms may apply for the media files.