Name: quantitative [18f]-naf-pet-mri analysis for the evaluation of dynamic bone turnover in a patient with facetogenic low back pain
Uploaded: 2019-08-08T11:45:00
Description: Watch this Scientific Journal Video about Quantitative [18F]-Naf-PET-MRI Analysis for the Evaluation of Dynamic Bone Turnover in a Patient with Facetogenic Low Back Pain at JoVE.com

Research support was provided by NIH P50AR060752 and GE Healthcare. We would like to acknowledge the support by Vahid Ravanfar.

This prospective feasibility study recruited patients after obtaining Human Study IRB approval and complying with HIPAA regulations.
1. Phantom
<ol>
	<li>Fill a hollow cylindrical phantom with an insert that has hollow cylinders with a range of diameters (5 -&#160;38 mm) with 185 MBq of [18F]-NaF.</li>
	<li>Generate an attenuation map of the phantom using CT or a template that was generated previously for this phantom.</li>
	<li>Place the phantom into the center of PET/MR and acqu...

<ol>
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E., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Tomographic+measurement+of+local+cerebral+glucose+metabolic+rate+in+humans+with+(F-18)2-fluoro-2-deoxy-D-glucose:+validation+of+method.">Tomographic measurement of local cerebral glucose metabolic rate in humans with (F-18)2-fluoro-2-deoxy-D-glucose: validation of method.</a> Annals of Neurology. 6 (5), 371-388 (1979).</li><li>Brenner, W., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Comparison+of+different+quantitative+approaches+to+18F-fluoride+PET+scans.">Comparison of different quantitative approaches to 18F-fluoride PET scans.</a> Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine. 45 (9), 1493-1500 (2004).</li><li>Schellinger, D., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Facet+joint+disorders+and+their+role+in+the+production+of+back+pain+and+sciatica.">Facet joint disorders and their role in the production of back pain and sciatica.</a> Radiographics: A Review Publication of the Radiological Society of North America, Inc. 7 (5), 923-944 (1987).</li><li>Schett, G. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Joint+remodelling+in+inflammatory+disease.">Joint remodelling in inflammatory disease.</a> Annals of the Rheumatic Diseases. 66, 42-44 (2007).</li><li>Baum, R., Gravallese, E. 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In this methodological manuscript, we have provided background on the potential utility of dynamic [18F]-NaF-PET-MRI for evaluating a wide range of bone pathologies and have outlined the techniques for dynamic [18F]-NaF-PET-MRI image acquisition and analysis using the human lumbar facet joints as prototypical regions of interest. Dual modality PET-MRI allows for acquisition of dynamic PET data over a time period similar to that required for MR data acquisition alone, thus maximizing the overlap of s...

Standard clinical imaging techniques of bone pathology are primarily limited to characterizing structural changes, which can be nonspecific. For example, asymptomatic morphologic abnormalities related to the normal aging may be indistinguishable from degenerative alterations which are responsible for severe pain and disability1. Bone is a dynamic tissue undergoing continuous remodeling with the competing activity of osteoblasts, which produce the new bone matrix, and osteoclasts, whose function is to eliminate mineralized bone2. [18F]-NaF is a positron emission tomography (PET) radiotracer that enables visualization of bone tissue metabolism. [18F]-NaF is chemically absorbed into hydroxyapatite in the bone matrix by osteoblasts and can thus noninvasively detect osteoblastic activity, thereby detecting a metabolic process which is occult to conventional imaging techniques. As a result, [18F]-NaF has been used for characterizing bone pathology in an increasing number of bone disorders including neoplasms, inflammatory, and degenerative disease of the bone and joints3,4,5.
PET data is most commonly analyzed in a semi-quantitative fashion, which can be readily performed in routine clinical practice with standardized uptake values (SUVs). As a metric, SUVs are useful to clinicians as they represent tissue uptake relative to the rest of the body6. Values from subsequent scans may be used to observe changes in uptake as a result of treatment or disease progression. The numerical nature of SUVs also aids in comparison between patients and between successive scans in the same patient. The algorithm used to calculate SUVs, Equation 1, makes the assumption that the tracer is equally distributed throughout the body and that the lean body mass accurately represents whole body volume. As such, SUVs are a semi-quantitative measurement. For a given region of interest (ROI), SUVmax (the maximum SUV value within a ROI), and SUVmean (the mean of all sampled SUVs within an ROI) are commonly used SUV metrics in clinical practice6.
Kinetic modeling of dynamic PET data can also be performed for more detailed quantitative analysis. While SUV data acquisition is static, kinetic modeling utilizes dynamic image data where tracer levels are continuously acquired providing a temporal dimension.&#160; From the more complex kinetic modeling of dynamic data, quantitative values and informative metrics of tracer dynamics can be extracted with respect to the measured activity in the image data. A sample two-tissue compartment model employed for dynamic kinetic modeling is shown in Figure 17. &#160;Cp is the concentration of tracer in the blood plasma while Ce and Ct represent the concentration in the unbound interstitial space and bound tracer in the target bone matrix respectively. K1, k2, k3, k4, are 4 rate parameters that describe the kinetic model for tracer wash in/out and binding. K1 describes the tracer taken up from arterial plasma into interstitial space (Ct), k2 describes the fraction of tracer that diffuses back from the interstitial space to plasma, k3 describes the tracer that moves from interstitial (Ce) space to bone (Ct), and k4 describes the tracer that moves from bone (Ct) back to the interstitial space (Ce).
<img alt="Figure 1" class="xfigimg" src="/files/ftp_upload/58491/58491fig1.jpg" /> 
Figure 1. A sample two-tissue compartment model for dynamic kinetic modeling. Cp is the tracer concentration in the blood plasma compartment, Ce free and non-specifically bound tracer concentration in tissue, and Ct specifically bound tracer concentration in the tissue. <a href="https://www.jove.com/files/ftp_upload/58491/58491fig1large.jpg" target="_blank">Please click here to view a larger version of this figure.</a>
The Patlak kinetic model produces Ki_Patlak as a measure of radiotracer influx rate (mL/ccm/min, cubic cm = ccm) from the blood pool into the bone matrix. The tracer influx rate from the blood pool to the bone matrix can then be calculated using Equation 2 and Equation 3 for Ki_Patlak and Ki_NonLinear respectively. Ki_Patlak and Ki_NonLinear are the rates at which [18F]-NaF leaves the arterial blood pool and irreversibly binds to a subsite bone matrix, using the two models respectively. A difference between the Patlak and non-linear kinetic model is in their utilization of the dynamic data. The Patlak model requires equilibrium to be met and then calculates the influx rate from the established linear slope. The Patlak kinetic model produces Ki_Patlak influx rates, by using a 24-minute time to equilibration of the plasma pool, Cp, to the unbound pool, Cu.&#160; The 24-minute time can change depending on the time found for all subsites to reach equilibration with the plasma pool in the sample. The more computationally rigorous non-linear model uses the entirety of the temporal data to fit a curve.
The goal of this methodological manuscript is to outline detailed techniques for performing dynamic [18F]-NaF-PET-MRI.&#160; The lumbar facet joint is a common site of degenerative arthritis disease and a common cause for axial low back pain8.&#160; Recent studies suggest [18F]-NaF-PET-MRI may serve as a useful biomarker of painful facetogenic disease9.&#160; The human lumbar facet joints from a single patient with facetogenic low back pain will thus be analyzed as a prototypical ROI for dynamic [18F]-NaF-PET-MRI analysis.

<table border="0" cellpadding="0" cellspacing="0" style="width:1045px;" width="1046">
	<colgroup>
		<col />
		<col />
		<col />
		<col />
	</colgroup>
	<tbody>
		<tr height="21">
			<td height="21" style="height:21px;width:307px;">Gadolinium Contrast agent (Gadovist)</td>
			<td style="width:211px;">Bayer</td>
			<td style="width:271px;">na</td>
			<td style="width:257px;">1.0mmol/ml solution for IV injection.</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:307px;">[18F]-NaF Radiotracer</td>
			<td style="width:211px;">na</td>
			<td style="width:271px;">na</td>
			<td>2.96 MBq/kg</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:307px;">GE Signa PET-MRI Scanner</td>
			<td style="width:211px;">General Electric</td>
			<td style="width:271px;">na</td>
			<td>3.0Tesla 60cm Bore PET-MRI scanner</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:307px;">PMOD Kinetic Modeling Software</td>
			<td style="width:211px;">PMOD Technologies, LLC</td>
			<td style="width:271px;">na</td>
			<td>Version 3.8</td>
		</tr>
	</tbody>
</table>

quantitative [18f]-naf-pet-mri analysis for the evaluation of dynamic bone turnover in a patient with facetogenic low back pain

Imaging techniques that reflect dynamic bone turnover may aid in characterizing a wide range of bone pathologies. Bone is a dynamic tissue undergoing continuous remodeling with the competing activity of osteoblasts, which produce the new bone matrix, and osteoclasts, whose function is to eliminate mineralized bone. [18F]-NaF is a positron emission tomography (PET) radiotracer that enables visualization of bone metabolism. [18F]-NaF is chemically absorbed into hydroxyapatite in the bone matrix by osteoblasts and can thus noninvasively detect osteoblastic activity, which is occult to conventional imaging techniques. Kinetic modeling of dynamic [18F]-NaF-PET data provides detailed quantitative measures of bone metabolism. Conventional semi-quantitative PET data, which utilizes standardized uptake values (SUVs) as a measure of radiotracer activity, is referred to as a static technique due to its snapshot of tracer uptake in time.&#160; Kinetic modeling, however, utilizes dynamic image data where tracer levels are continuously acquired providing tracer uptake temporal resolution. From the kinetic modeling of dynamic data, quantitative values like blood flow and metabolic rate (i.e., potentially informative metrics of tracer dynamics) can be extracted, all with respect to the measured activity in the image data. When combined with dual modality PET-MRI, region-specific kinetic data can be correlated with anatomically registered high-resolution structural and pathologic information afforded by MRI. The goal of this methodological manuscript is to outline detailed techniques for performing and analyzing dynamic [18F]-NaF-PET-MRI data. The lumbar facet joint is a common site of degenerative arthritis disease and a common cause for axial low back pain.&#160; Recent studies suggest [18F]-NaF-PET may serve as a useful biomarker of painful facetogenic disease.&#160; The human lumbar facet joint will, therefore, be used as a prototypical region of interest for dynamic [18F]-NaF-PET-MRI analysis in this manuscript.

18NaF-PET uptake values are measured in the bilateral facet joints at the L1-L2 through L5-S1 vertebral levels for a total of 10 ROIs in a single representative patient with axial low back pain. Representative [18F]-NaF-PET, axial T2 fat suppressed, and axial T1 post-contrast fat-suppressed MR images through the level of the L3-L4 facet joints are shown in Figure 2.&#160; The Ki_Patlak, SUVmean, SUVmax, and MRI facet arthropathy grade fo...

Watch this Scientific Journal Video about Quantitative [18F]-Naf-PET-MRI Analysis for the Evaluation of Dynamic Bone Turnover in a Patient with Facetogenic Low Back Pain at JoVE.com

Quantitative [18F]-Naf-PET-MRI Analysis for the Evaluation of Dynamic Bone Turnover in a Patient with Facetogenic Low Back Pain

Imaging techniques that reflect dynamic bone turnover may aid in characterizing a wide range of bone pathologies. We present detailed methodologies for performing and analyzing dynamic [18F]-NaF-PET-MRI data in a patient with facetogenic low back pain using the lumbar facet joints as a prototypical region of interest.

Quantitative [18F]-Naf-PET-MRI Analysis for the Evaluation of Dynamic Bone Turnover in a Patient with Facetogenic Low Back Pain

Imaging techniques that reflect dynamic bone turnover may aid in characterizing a wide range of bone pathologies. Bone is a dynamic tissue undergoing ...

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