On transcending the impasse of respiratory motion correction applications in routine clinical imaging - a consideration of a fully automated data driven motion control framework.

Positron emission tomography (PET) is increasingly used for the detection, characterization, and follow-up of tumors located in the thorax. However, patient respiratory motion presents a unique limitation that hinders the application of high-resolution PET technology for this type of imaging. Efforts to transcend this limitation have been underway for more than a decade, yet PET remains for practical considerations a modality vulnerable to motion-induced image degradation. Respiratory motion control is not employed in routine clinical operations. In this article, we take an opportunity to highlight some of the recent advancements in data-driven motion control strategies and how they may form an underpinning for what we are presenting as a fully automated data-driven motion control framework. This framework represents an alternative direction for future endeavors in motion control and can conceptually connect individual focused studies with a strategy for addressing big picture challenges and goals.

Comparing approaches to correct for respiratory motion in NH3 PET-CT cardiac perfusion imaging.

AIM: Respiratory motion affects cardiac PET-computed tomography (CT) imaging by reducing attenuation correction (AC) accuracy and by introducing blur. The aim of this study was to compare three approaches for reducing motion-induced AC errors and evaluate the inclusion of respiratory motion correction. MATERIALS AND METHODS: AC with a helical CT was compared with averaged cine and gated cine CT, as well as with a pseudo-gated CT, which was produced by applying PET-derived motion fields to the helical CT. Data-driven gating was used to produce respiratory-gated PET and CT images, and 60 NH3 PET scans were attenuation corrected with each of the CTs. Respiratory motion correction was applied to the gated and pseudo-gated attenuation-corrected PET images. RESULTS: Anterior and lateral wall intensity measured in attenuation-corrected PET images generally increased when PET-CT alignment improved and decreased when alignment degraded. On average, all methods improved PET-CT liver and cardiac alignment, and increased anterior wall intensity by more than 10% in 36, 33 and 25 cases for the averaged, gated and pseudo-gated CTAC PET images, respectively. However, cases were found where alignment worsened and severe artefacts resulted. This occurred in more cases and to a greater extent for the averaged and gated CT, where the anterior wall intensity reduced by more than 10% in 21 and 24 cases, respectively, compared with six cases for the pseudo-gated CT. Application of respiratory motion correction increased the average anterior and inferior wall intensity, but only 13% of cases increased by more than 10%. CONCLUSION: All methods improved average respiratory-induced AC errors; however, some severe artefacts were produced. The pseudo-gated CT was found to be the most robust method.

¹8F-fluoride PET as a noninvasive imaging biomarker for determining treatment efficacy of bone active agents at the hip: a prospective, randomized, controlled clinical study.

The functional imaging technique of ¹8F-fluoride positron emission tomography (¹8F-PET) allows the noninvasive quantitative assessment of regional bone formation at any skeletal site, including the spine and hip. The aim of this study was to determine if ¹8F-PET can be used as an early biomarker of treatment efficacy at the hip. Twenty-seven treatment-naive postmenopausal women with osteopenia were randomized to receive teriparatide and calcium and vitamin D (TPT group, n = 13) or calcium and vitamin D only (control group, n = 14). Subjects in the TPT group were treated with 20 µg/day teriparatide for 12 weeks. ¹8F-PET scans of the proximal femur, pelvis, and lumbar spine were performed at baseline and 12 weeks. The plasma clearance of ¹8F-fluoride to bone, K(i), a validated measurement of bone formation, was measured at four regions of the hip, lumbar spine, and pelvis. A significant increase in K(i) was observed at all regions of interest (ROIs), including the total hip (+27%, p = 0.002), femoral neck (+25%, p = 0.040), hip trabecular ROI (+21%, p = 0.017), and hip cortical ROI (+51%, p = 0.001) in the TPT group. Significant increases in K(i) in response to TPT were also observed at the lumbar spine (+18%, p = 0.001) and pelvis (+42%, p = 0.001). No significant changes in K(i) were observed for the control group. Changes in BMD and bone turnover markers were consistent with previous trials of teriparatide. In conclusion, this is the first study to our knowledge to demonstrate that ¹8F-PET can be used as an imaging biomarker for determining treatment efficacy at the hip as early as 12 weeks after initiation of therapy.

The precision and sensitivity of (18)F-fluoride PET for measuring regional bone metabolism: a comparison of quantification methods.

UNLABELLED: The planning of research studies requires an understanding of the minimum number of subjects required. The aim of this study was to evaluate different methods of analyzing (18)F-fluoride PET ((18)F(-) PET) dynamic spine scans to find the approach that requires the smallest sample size to detect a statistically significant response to treatment. METHODS: Eight different approaches to (18)F(-) PET analysis (3 variants of the Hawkins 3-tissue compartmental model, 3 variants of spectral analysis, deconvolution, and Patlak analysis) were used to evaluate the fluoride plasma clearance to bone mineral (K(i)). Standardized uptake values (SUVs) were also studied. Data for 20 women who had (18)F(-) PET spine scans at 0, 6, and 12 mo after stopping long-term bisphosphonate treatment were used to compare precision errors. Data for 18 women who had scans at baseline and 6 mo after starting teriparatide treatment were used to compare response to treatment. RESULTS: The 4 approaches that fitted the rate constant k(4) describing the reverse flow of (18)F from bone as a free variable showed close agreement in K(i) values, with correlation coefficients greater than 0.97. Their %CVs were 14.4%-14.8%, and treatment response to teriparatide was 23.2%-23.8%. The 3 methods that assumed k(4) = 0 gave K(i) values 20%-25% lower than the other methods, with correlation coefficients of 0.83-0.94, percentage coefficients of variation (%CVs) of 12.9%-13.3%, and treatment response of 25.2%-28.3%. A Hawkins model with k(4) = 0.01 min(-1) did not perform any better (%CV, 14.2%; treatment response, 26.1%). Correlation coefficients between SUV and the different K(i) methods varied between 0.60 and 0.65. Although SUV gave the best precision (%CV, 10.1%), the treatment response (3.1%) was not statistically significant. CONCLUSION: Methods that calculated K(i) assuming k(4) = 0 required fewer subjects to demonstrate a statistically significant response to treatment than methods that fitted k(4) as a free variable. Although SUV gave the smallest precision error, the absence of any significant changes make it unsuitable for examining response to treatment in this study.

Extension of a data-driven gating technique to 3D, whole body PET studies.

Respiratory gating can be used to separate a PET acquisition into a series of near motion-free bins. This is typically done using additional gating hardware; however, software-based methods can derive the respiratory signal from the acquired data itself. The aim of this work was to extend a data-driven respiratory gating method to acquire gated, 3D, whole body PET images of clinical patients. The existing method, previously demonstrated with 2D, single bed-position data, uses a spectral analysis to find regions in raw PET data which are subject to respiratory motion. The change in counts over time within these regions is then used to estimate the respiratory signal of the patient. In this work, the gating method was adapted to only accept lines of response from a reduced set of axial angles, and the respiratory frequency derived from the lung bed position was used to help identify the respiratory frequency in all other bed positions. As the respiratory signal does not identify the direction of motion, a registration-based technique was developed to align the direction for all bed positions. Data from 11 clinical FDG PET patients were acquired, and an optical respiratory monitor was used to provide a hardware-based signal for comparison. All data were gated using both the data-driven and hardware methods, and reconstructed. The centre of mass of manually defined regions on gated images was calculated, and the overall displacement was defined as the change in the centre of mass between the first and last gates. The mean displacement was 10.3 mm for the data-driven gated images and 9.1 mm for the hardware gated images. No significant difference was found between the two gating methods when comparing the displacement values. The adapted data-driven gating method was demonstrated to successfully produce respiratory gated, 3D, whole body, clinical PET acquisitions.

Differential effects of teriparatide on regional bone formation using (18)F-fluoride positron emission tomography.

Teriparatide increases skeletal mass, bone turnover markers, and bone strength, but local effects on bone tissue may vary between skeletal sites. We used positron emission tomography (PET) to study (18)F-fluoride plasma clearance (K(i)) at the spine and standardized uptake values (SUVs) at the spine, pelvis, total hip, and femoral shaft in 18 postmenopausal women with osteoporosis. Subjects underwent a 1-hour dynamic scan of the lumbar spine and a 10-minute static scan of the pelvis and femurs at baseline and after 6 months of treatment with 20 µg/day teriparatide. Blood samples were taken to derive the arterial input function and lumbar spine K(i) values evaluated using a three-compartment model. SUVs were calculated for the spine, pelvis, total hip, and femoral shaft. After 6 months treatment with teriparatide, spine K(i) values increased by 24% (p = .0003), while other model parameters were unchanged except for the fraction of tracer going to bone mineral (k(3)/[k(2) + k(3)]), which increased by 23% (p = .0006). In contrast to K(i) , spine SUVs increased by only 3% (p = .84). The discrepancy between changes in K(i) and SUVs was explained by a 20% decrease in (18)F(-) plasma concentration. SUVs increased by 37% at the femoral shaft (p = .0019), 20% at the total hip (p = .032), and 11% at the pelvis (p = .070). Changes in bone turnover markers and BMD were consistent with previous trials. We conclude that the changes in bone formation rate during teriparatide treatment as measured by (18)F(-) PET differ at different skeletal sites, with larger increases in cortical bone than at trabecular sites.

The effect of inaccurate bone attenuation coefficient and segmentation on reconstructed PET images.

OBJECTIVE: Combined PET/MRI scanners will require the use of MR images to attenuation correct the PET acquisition. A recognised issue with this is the lack of bone signal in conventional MR images. One approach is to segment the MRI and use a constant attenuation coefficient in place of the bone. The aim of this study was to investigate the effect of replacing the attenuation coefficients of the bone with various constant values on PET. METHODS: Bone segmentation was performed on the computed tomography (CT) components of PET/CT images from nine patients, and the bone replaced with three patient-specific values and three generic values. Attenuation-corrected PET images were reconstructed using the modified CT data and compared with the PET images reconstructed using the original CT data. The resulting effects on regions of interest measurements and in all chest voxels were evaluated. RESULTS: Replacing the bone with the mean bone value (patient specific) produced the least error with, on an average, a maximum error in the lung of 5%. Of the generic bone replacement values tested, an overestimated bone volume with soft tissue values produced the lowest error with, on an average, up to 36, 20 and 10% error in the bone, soft tissue and lung, respectively. CONCLUSION: When the bones are substituted with attenuation coefficients that are higher than the soft-tissue, variations in bone classification can significantly degrade the PET images. Using an overestimated bone volume consisting of soft tissue equivalent attenuation coefficients presents a simple, robust method that is less sensitive to segmentation errors.

Retrospective data-driven respiratory gating for PET/CT.

Respiratory motion can adversely affect both PET and CT acquisitions. Respiratory gating allows an acquisition to be divided into a series of motion-reduced bins according to the respiratory signal, which is typically hardware acquired. In order that the effects of motion can potentially be corrected for, we have developed a novel, automatic, data-driven gating method which retrospectively derives the respiratory signal from the acquired PET and CT data. PET data are acquired in listmode and analysed in sinogram space, and CT data are acquired in cine mode and analysed in image space. Spectral analysis is used to identify regions within the CT and PET data which are subject to respiratory motion, and the variation of counts within these regions is used to estimate the respiratory signal. Amplitude binning is then used to create motion-reduced PET and CT frames. The method was demonstrated with four patient datasets acquired on a 4-slice PET/CT system. To assess the accuracy of the data-derived respiratory signal, a hardware-based signal was acquired for comparison. Data-driven gating was successfully performed on PET and CT datasets for all four patients. Gated images demonstrated respiratory motion throughout the bin sequences for all PET and CT series, and image analysis and direct comparison of the traces derived from the data-driven method with the hardware-acquired traces indicated accurate recovery of the respiratory signal.