Brad J. Kemp

Background: Post-treatment prognosis and monitoring are critical for determining the timing of salvage treatment in glioblastoma patients but has been challenging due to difficulties differentiating progression from treatment effects in conventional images. This exploratory study aimed to establish the correlation of radiomics image features from time series of amino acid tracer ¹⁸F-DOPA PET images, with outcomes, using machine learning and dimension reduction analysis. Methods: ¹⁸F-DOPA PET images were collected for a patient cohort with wild-type IDH and unmethylated MGMT who underwent dose-escalated radiation therapy. Quantitative features were derived from the high uptake region (T/N > 2.0) in pre- and post-radiation therapy follow-up ¹⁸F-DOPA PET images. A customized workflow was utilized for pre-selecting predictive features, followed by manifold learning. Machine learning algorithms were employed to establish associations between imaging features and remaining survival (RS), defined as the time between a follow-up scan and date of death. Results: The ML models exhibited 81–83% ROC_AUC in predicting RS evaluated on an independent test dataset. A RS map is proposed for monitoring tumor alterations through serial ¹⁸F-DOPA PET scans, demonstrating superior sensitivity and better correlation with survival compared to the RANO criteria. Conclusions: Our study demonstrates that ML models utilizing FU ¹⁸F-DOPA PET images have the potential to effectively predict future survival outcomes in patients with glioblastoma treated with dose-escalated radiation therapy. The capability to assess changes in tumor over time through imaging can potentially assist in patient stratification and the selection of salvage treatments, while also aiding in distinguishing treatment effects from genuine tumor progression.

BACKGROUND AND PURPOSE: Prior retrospective studies have suggested that both T2 hyperintensity and gadolinium enhancement on fat-suppressed MR imaging are associated with lumbar facet joint pain, but prospective evaluation of FDG-PET/MR imaging with a standardized protocol and correlation to clinical findings are lacking. The primary aim was to prospectively assess a standardized FDG-PET/MRI protocol in patients with suspected facetogenic low back pain, with determination of the concordance of imaging and clinical findings. MATERIALS AND METHODS: Ten patients with clinically suspected facetogenic low back pain were prospectively recruited with a designation of specific facet joints implicated clinically. Subsequently, patients underwent an FDG-PET/MR imaging examination with gadolinium. Each facet joint was graded for perifacet signal change on MR imaging and FDG activity. The frequency and correlation of MR imaging, FDG-PET, and clinical findings were determined. RESULTS: FDG activity showed high concordance with high overall MR imaging scores (concordance correlation coefficient = 0.79). There was concordance of the clinical side of pain with the side of high overall MR imaging scores and increased FDG activity on 12/20 (60%) sides. Both a high overall MR imaging score (concordance correlation coefficient = 0.12) and FDG-PET findings positive for increased activity (concordance correlation coefficient = 0.10) had low concordance with the specific clinically implicated facet joints. Increased FDG activity or high MR imaging scores or both were present in only 10/29 (34%) facet joints that had been clinically selected for percutaneous intervention. Eleven (11%) facet joints that had not been selected for treatment demonstrated these imaging findings. CONCLUSIONS: There was low concordance of perifacet signal change and FDG activity with clinically implicated facet joints. This could indicate either the potential to change patient management or a lack of biomarker accuracy. Therefore, additional larger randomized studies with the use of comparative medial branch blocks would be useful to further investigate the clinical utility of these findings.

A standardised method for quantifying β-amyloid PET tracers would allow comparison across different tracers and different sites. The development of the Centiloid scale has aimed to achieve this, applying a common scale to better aid the diagnosis and prognosis of Alzheimer’s disease (AD) and to monitor anti-amyloid therapeutic interventions. Here, we apply the Centiloid method to [18F]flutemetamol and [11C]PiB (PiB, Pittsburgh compound B) PET images and derive the scaling factor to express their binding in Centiloids. Paired PiB and [18F]flutemetamol scans for 74 subjects, including 24 young healthy controls (37 ± 5 years), were analysed using the standard Centiloid method. The same subjects were also analysed using PMOD- and FSL-based pipelines as well as SPM8. Test-retest analysis of 10 AD subjects was also performed with each pipeline. The standard uptake value ratios (SUVR), determined using the standard SPM8 Centiloid process, showed a strong correlation between [18F]flutemetamol (Flute) and PiB binding (SUVR-Flute = 0.77 × SUVR-PiB + 0.22, R2 = 0.96). Application of the standard Centiloid process allowed the calculation of a direct conversion equation for SUVR-Flute to Centiloid units (CL) (CL = (121.42*SUVR-Flute) − 121.16). Analysis of the data via the two alternate Centiloid pipelines allowed us to derive standardised, SPM8-equivalent equations for both PMOD (CL = (115.24*SUVR-Flute) − 107.86) and FSL (CL = (120.32*SUVR-Flute) − 112.75) respectively. Test-retest analysis of 10 AD subjects showed an approximate 2% difference for each pipeline. [18F]flutemetamol data can now be expressed in Centiloid units, enhancing its utility in clinical and research applications for β-amyloid imaging. The standard Centiloid method also demonstrates that [18F]flutemetamol has favourable performance compared with PiB and other β-amyloid tracers. Test-retest difference averaged 2%, with no difference between image processing pipelines. Centiloid scaling is robust and can be implemented on a number of platforms.

18F-Tetrafluoroborate (18F-TFB) is a promising iodide analog for PET imaging of thyroid cancer and sodium/iodide symporter (NIS) reporter activity in viral therapy applications. The aim of this study was to evaluate the safety, pharmacokinetics, biodistribution, and radiation dosimetry of high-specific activity 18F-TFB in healthy human subjects. 18F-TFB was synthesized with specific activity of 3.2 ± 1.3 GBq/μmol (at the end of synthesis). Dynamic and whole-body static PET/CT scans over 4 h were performed after intravenous administration of 18F-TFB (333–407 MBq) in four female and four male healthy volunteers (35 ± 11 years old). Samples of venous blood and urine were collected over the imaging period and analyzed by ion-chromatography HPLC to determine tracer stability. Vital signs and clinical laboratory safety assays were measured to evaluate safety. 18F-TFB administration was well tolerated with no significant findings on vital signs and no clinically meaningful changes in clinical laboratory assays. Left-ventricular blood pool time-activity curves showed a multi-phasic blood clearance of 18F-radioactivity with the two rapid clearance phases over the first 20 min, followed by a slower clearance phase. HPLC analysis showed insignificant 18F-labeled metabolites in the blood and urine over the length of the study (4 h). High uptakes were seen in the thyroid, stomach, salivary glands, and bladder. Urinary clearance of 18F-TFB was prominent. Metabolic stability was evidenced by low accumulation of 18F-radioactivity in the bone. Effective doses were 0.036 mSv/MBq in males and 0.064 mSv/MBq in females (p = 0.08, not significant). This initial study in healthy human subjects showed 18F-TFB was safe and distributed in the human body similar to other iodide analogs. These data support further translational studies with 18F-TFB as NIS gene reporter and imaging biomarker for thyroid cancer and other disease processes that import iodide.

National Electrical Manufacturers Association (NEMA) NU 2-2007 performance measurements were conducted on the Inveon preclinical small animal PET system developed by Siemens Medical Solutions. The scanner uses 1.51 x 1.51 x 10 mm LSO crystals grouped in 20 x 20 blocks; a tapered light guide couples the LSO crystals of a block to a position-sensitive photomultiplier tube. There are 80 rings with 320 crystals per ring and the ring diameter is 161 mm. The transaxial and axial fields of view (FOVs) are 100 and 127 mm, respectively. The scanner can be docked to a CT scanner; the performance characteristics of the CT component are not included herein. Performance measurements of spatial resolution, sensitivity, scatter fraction and count rate performance were obtained for different energy windows and coincidence timing window widths. For brevity, the results described here are for an energy window of 350-650 keV and a coincidence timing window of 3.43 ns. The spatial resolution at the center of the transaxial and axial FOVs was 1.56, 1.62 and 2.12 mm in the tangential, radial and axial directions, respectively, and the system sensitivity was 36.2 cps kBq(-1) for a line source (7.2% for a point source). For mouse- and rat-sized phantoms, the scatter fraction was 5.7% and 14.6%, respectively. The peak noise equivalent count rate with a noisy randoms estimate was 1475 kcps at 130 MBq for the mouse-sized phantom and 583 kcps at 74 MBq for the rat-sized phantom. The performance measurements indicate that the Inveon PET scanner is a high-resolution tomograph with excellent sensitivity that is capable of imaging at a high count rate.

The National Electrical Manufacturers Association (NEMA) NU 2-2001 performance measurements were conducted on the Discovery RX, a whole-body PET/CT system under development by GE Healthcare. The PET scanner uses 4.2 x 6.3 x 30 mm lutetium yttrium orthosilicate (LYSO) crystals grouped in 9 x 6 blocks. There are 24 rings with 630 crystals per ring and the ring diameter is 88.6 cm. The transaxial and axial fields of view are 70.0 and 15.7 cm, respectively. The scanner has retractable septa and can operate in both 2-dimensional (2D) and 3-dimensional (3D) modes. 2D acquisitions use ring differences of +/-4 for direct and +/-5 for cross slices; 3D acquisitions use a ring difference of 23. The coincident window width is 6.5 ns and the energy window is 425-650 keV. Other than the detectors, the system uses the same hardware and software as a Discovery ST. The CT scanner is a 16-slice LightSpeed; the performance characteristics of the CT component are not included herein. Performance measurements of sensitivity, spatial resolution, image quality, scatter fraction and counting rate performance, and image quality were obtained using NEMA methodology. The system sensitivity in 2D and 3D was measured as 1.7 cps/kBq and 7.3 cps/kBq, respectively. The transaxial resolution for 2D (3D) was 5.1 mm full width at half maximum (FWHM) (5.0 mm) at 1 cm from gantry center and the radial and tangential resolutions were 5.9 mm (5.9 mm) and 5.1 mm (5.2 mm) at 10 cm, respectively. The axial resolution for 2D (3D) was 4.8 mm FWHM (5.8 mm) and 6.3 mm (6.5 mm) at 1 cm and 10 cm from gantry center, respectively. The scatter fraction was 13.1% and 31.8% in 2D and 3D. The peak noise equivalent count rate (NECR) was 155 kcps at 92.1 kBq/mL in 2D and 117.7 kcps at 21.7 kBq/mL in 3D for a noise-free estimation of randoms. The contrast of the 22, 17, 13, and 10 mm hot spheres in the image quality phantom in 2D (3D) were 74.6% (72.4%), 56.7% (59.5%), 46.2% (44.6%), and 17.9% (18.0%), respectively. The Discovery RX is a scanner that possesses high NECR, low scatter fraction, and good spatial resolution characteristics.