Gamma camera-specific reference standards for radioactive iodine uptake measurements.

BACKGROUND: Current guidelines of the radioiodine uptake (RAIU) test allow the use of different equipment, isotopes, activity and region-of-interest (ROI). We evaluated presence and extent of these differences in clinical practice and evaluated the effect of some of these variations on RAIU outcomes. Also, gamma camera-specific reference standards were calculated and retrospectively compared with measurements obtained during clinical RAIU tests. MATERIALS AND METHODS: First, questionnaires were sent to Dutch nuclear medicine departments requesting information about equipment usage, isotope, isotope formulation, activity and measurement techniques. Secondly, a neck phantom containing a range of activities in capsule or water-dissolved formulation was scanned. Counts were measured using automatic ROI, square box ROI or all counts in the image. Thirdly, clinical RAIU data were collected during 2015-2018 using three different gamma cameras. Reference standards for each scanner were calculated using regression analysis between reference activity and measured counts. Uptake measurements using this gamma camera-specific reference standard were compared with original measurements. RESULTS: The survey demonstrated significant differences in isotope, isotope formulation, activity, use of neck phantoms, frequency and duration of reference measurements, distance to collimator, use of background measurements and ROI delineation. The phantom study demonstrated higher counts for the water-dissolved formulation than capsules using both automatic and square box ROI. Also, higher counts were found using a square box ROI than an automatic ROI. The retrospective study showed feasibility of RAIU calculations using camera-specific reference standards and good correlation with the original RAIU measurements. CONCLUSIONS: This study demonstrated considerable technical variation in RAIU measurement in clinical practice. The phantom study demonstrated that these differences could result in differences in count measurements, potentially resulting in different dose calculations for radioactive iodine therapy. Retrospective data suggest that camera-specific reference standards may be used instead of individual reference measurements using separate activity sources, which may thus eliminate some sources of variation.

Randomized controlled trial comparing magnetic marker localization (MaMaLoc) with wire-guided localization in the treatment of early-stage breast cancer.

Wire-guided localization (WGL) is the standard of care in the surgical treatment of nonpalpable breast tumors. In this study, we compare the use of a new magnetic marker localization (MaMaLoc) technique to WGL in the treatment of early-stage breast cancer patients. Open-label, single-center, randomized controlled trial comparing MaMaLoc (intervention) to WGL (control) in women with early-stage breast cancer. Primary outcome was surgical usability measured using the System Usability Scale (SUS, 0-100 score). Secondary outcomes were patient reported, clinical, and pathological outcomes such as retrieval rate, operative time, resected specimen weight, margin status, and reoperation rate. Thirty-two patients were analyzed in the MaMaLoc group and 35 in the WGL group. Patient and tumor characteristics were comparable between groups. No in situ complications occurred. Retrieval rate was 100% in both groups. Surgical usability was higher for MaMaLoc: 70.2 ± 8.9 vs. 58.1 ± 9.1, p < 0.001. Patients reported higher overall satisfaction with MaMaLoc (median score 5/5) versus WGL (score 4/5), p < 0.001. The use of magnetic marker localization (MaMaLoc) for early-stage breast cancer is effective and has higher surgical usability than standard WGL.

Estimation of detection limits of a clinical fluorescence optical mammography system for the near-infrared fluorophore IRDye800CW: phantom experiments.

To evaluate if clinical fluorescence imaging of IRDye800CW is feasible on our fluorescence optical mammography system by estimating detection limits assessed by breast-cancer-simulating phantom experiments. Phantoms (2.1 cm(3), 0.9 cm(3)) with IRDye800CW concentrations of 0.5 to 120 nM were suspended in a 550 cm(3) measurement cup containing 507 surface-mounted source and detector fibers. The cup was filled with optical matching fluid containing IRDye800CW concentrations of 0, 5, 10, or 20 nM. Tomographic fluorescence images were acquired by exciting IRDye800CW at 730 nm; wavelengths above 750 nm were filtered. Signal intensities were calculated over a volume of interest corresponding to the size and location of the phantom in the reconstructed images. Correlations (R(2)) were calculated, and detection limits with associated upper 95% prediction interval were estimated. Between-day reproducibility was assessed with intraclass correlation coefficients (ICC). Fluorescent intensities were strongly correlated with phantom IRDye800CW concentrations (R(2)0.983 to 0.999). IRDye800CW detection limits ranged from 0.14 to 2.46 nM (upper 95% prediction limit 4.63 to 18.63 nM). ICC ranged from 0.88 to 1.00. The estimated detection limits for IRDye800CW were in the low-nanomolar range. These results support the start of clinical trials to evaluate the fluorescence optical mammography system using IRDye800CW labeled breast cancer targeting ligands.

Magnetic resonance compatibility of intraocular lenses measured at 7 Tesla.

PURPOSE: To determine whether intraocular lenses (IOLs) are compatible with magnetic resonance imaging (MRI) at a magnetic field strength of 7 Tesla, the highest field strength at which clinical MRI scans are performed. METHODS: A set of 23 intraocular lenses was selected based on the presence of dyes and metals and different geometric shapes. MR compatibility was evaluated in a high-field 7-Tesla MRI scanner according to the American Standard Test Method (ASTM). The magnetically induced displacement was measured via the angular deflection method. The degree of magnetic susceptibility artifact formation was evaluated by positioning the IOLs in a phantom gel for scanning, using a three-dimensional gradient echo (GRE) sequence. All images were visually inspected to determine the spatial extent of any signal voids. Fiber-optic temperature probes were deployed to measure radio-frequency (RF) heating using a GRE sequence with powers 10 times higher than clinical settings. RESULTS: No significant displacement was detected with any of the tested IOLs. A significant magnetic susceptibility artifact was caused by the small platinum component of the Worst Platinum Clip IOL. None of the other 22 IOLs caused measurable susceptibility artifacts. Measurements on RF-induced heating showed no significant temperature rise (<0.25°C) of the tested IOLs. CONCLUSIONS: MRI did not induce movement or RF heating of any of the IOLs. We conclude that all the tested intraocular lenses are considered safe for MRI up to and including 7 Tesla. One IOL, the Worst Platinum Clip IOL, caused a significant imaging artifact.

Image derived input functions: effects of motion on tracer kinetic analyses.

PURPOSE: To quantify the effects of motion affected image-derived input functions (IDIF) on the outcome of tracer kinetic analyses. PROCEDURES: Two simulation studies, one based on high and the other on low cortical uptake, were performed. Different degrees of rotational and axial translational motion were added to the final frames of simulated dynamic positron emission tomography scans. Extracted IDIFs from motion affected simulated scans were compared to original IDIFs and to outcome of tracer kinetic analysis (volume of distribution, V (T)). RESULTS: Differences in IDIF values of up to 239% were found for the last frames. Patient motion of more than 6° or 5 mm resulted in at least 10% higher or lower V (T) values for the high cortical tracer. CONCLUSION: The degrees of motion studied are commonly observed in clinical studies and hamper the extraction of accurate IDIFs. Therefore, it is essential to ensure that patient motion is minimal and corrected for.

In vivo validation of reconstruction-based resolution recovery for human brain studies.

The aim of this study was to validate in vivo the accuracy of a reconstruction-based partial volume correction (PVC), which takes into account the point spread function of the imaging system. The NEMA NU2 Image Quality phantom and five healthy volunteers (using [(11)C]flumazenil) were scanned on both HR+ and high-resolution research tomograph (HRRT) scanners. HR+ data were reconstructed using normalization and attenuation-weighted ordered subsets expectation maximization (NAW-OSEM) and a PVC algorithm (PVC-NAW-OSEM). HRRT data were reconstructed using 3D ordinary Poisson OSEM (OP-OSEM) and a PVC algorithm (PVC-OP-OSEM). For clinical studies, parametric volume of distribution (V(T)) images were generated. For phantom data, good recovery was found for both OP-OSEM (0.84 to 0.97) and PVC-OP-OSEM (0.91 to 0.98) HRRT reconstructions. In addition, for the HR+, good recovery was found for PVC-NAW-OSEM (0.84 to 0.94), corresponding well with OP-OSEM. Finally, for clinical data, good correspondence was found between PVC-NAW-OSEM and OP-OSEM-derived V(T) values (slope: 1.02+/-0.08). This study showed that HR+ image resolution using PVC-NAW-OSEM was comparable to that of the HRRT scanner. As the HRRT has a higher intrinsic resolution, this agreement validates reconstruction-based PVC as a means of improving the spatial resolution of the HR+ scanner and thereby improving the quantitative accuracy of positron emission tomography.

Off-line motion correction methods for multi-frame PET data.

PURPOSE: Patient motion during PET acquisition may affect measured time-activity curves, thereby reducing accuracy of tracer kinetic analyses. The aim of the present study was to evaluate different off-line frame-by-frame methods to correct patient motion, which is of particular interest when no optical motion tracking system is available or when older data sets have to be reanalysed. METHODS: Four different motion correction methods were evaluated. In the first method attenuation-corrected frames were realigned with the summed image of the first 3 min. The second method was identical, except that non-attenuation-corrected images were used. In the third and fourth methods non-attenuation-corrected images were realigned with standard and cupped transmission images, respectively. Two simulation studies were performed, based on [11C]flumazenil and (R)-[11C]PK11195 data sets, respectively. For both simulation studies different types (rotational, translational) and degrees of motion were added. Simulated PET scans were corrected for motion using all correction methods. The optimal method derived from these simulation studies was used to evaluate two (one with and one without visible movement) clinical data sets of [11C]flumazenil, (R)-[11C]PK11195 and [11C]PIB. For these clinical data sets, the volume of distribution (VT) was derived using Logan analysis and values were compared before and after motion correction. RESULTS: For both [11C]flumazenil and (R)-[11C]PK11195 simulation studies, optimal results were obtained when realignment was based on non-attenuation-corrected images. For the clinical data sets motion disappeared visually after motion correction. Regional differences of up to 433% in VT before and after motion correction were found for scans with visible movement. On the other hand, when no visual motion was present in the original data set, overall differences in VT before and after motion correction were <1.5 ± 1.3%. CONCLUSION: Frame-by-frame motion correction using non-attenuation-corrected images improves the accuracy of tracer kinetic analysis compared to non-motion-corrected data. Electronic supplementary material The online version of this article (doi:10.1007/s00259-009-1193-y) contains supplementary material, which is available to authorised users.

Image-derived input functions for PET brain studies.

PURPOSE: To assess the robustness of a previously introduced method to obtain accurate image-derived input functions (IDIF) for three other tracers. METHODS: Dynamic PET and online blood data of five repeat [(11)C]PIB (Pittsburgh Compound-B) ([(11)C]PIB), six repeat (R)-[(11)C]verapamil, and ten single (R)-[(11)C]PK11195 studies were used. IDIFs were extracted from partial volume corrected scans using the four hottest pixels per plane method. Results obtained with IDIFs were compared with those using standard online measured arterial input functions (BSIF). IDIFs were used both with and without calibration based on manual blood samples. RESULTS: For (R)-[(11)C]verapamil, accurate IDIFs were obtained using noncalibrated IDIFs (slope 0.96+/-0.17; R (2) 0.92+/-0.07). However, calibration was necessary to obtain IDIFs comparable to the BSIF for both [(11)C]PIB (slope 1.04+/-0.05; R (2) 1.00+/-0.01) and (R)-[(11)C]PK11195 (slope 0.96+/-0.05; R (2) 0.99+/-0.01). The need for calibration may be explained by the sticking property of both tracers, indicating that BSIF may be affected by sticking and therefore may be unreliable. CONCLUSION: The present study shows that a previously proposed method to extract IDIFs is suitable for analysing [(11)C]PIB, (R)-[(11)C]verapamil and (R)-[(11)C]PK11195 studies, thereby obviating the need for online arterial sampling.

Image derived input functions for dynamic High Resolution Research Tomograph PET brain studies.

The High Resolution Research Tomograph (HRRT) is a dedicated human brain positron emission tomography (PET) scanner. The aim of the present study was to validate the use of image derived input functions (IDIF) as an alternative for arterial sampling for HRRT human brain studies. To this end, IDIFs were extracted from 3D ordinary Poisson ordered subsets expectation maximization (OP-OSEM) and reconstruction based partial volume corrected (PVC) OP-OSEM images. IDIFs, either derived directly from regions of interest or further calibrated using manual samples taken during scans, were evaluated for dynamic [(11)C]flumazenil data (n=6). Results obtained with IDIFs were compared with those obtained using blood sampler input functions (BSIF). These comparisons included areas under the curve (AUC) for peak (0-3.3 min) and tail (3.3-55.0 min). In addition, slope, intercept and Pearson's correlation coefficient of tracer kinetic analysis results based on IDIF and BSIF were calculated for each subject. Good peak AUC ratios (0.83+/-0.21) between IDIF and BSIF were found for calibrated IDIFs extracted from OP-OSEM images. This combination of IDIFs and images also provided good slope values (1.07+/-0.11). Improved resolution, as obtained with PVC OP-OSEM, changed AUC ratios to 1.14+/-0.35 and, for tracer kinetic analysis, slopes changed to 0.95+/-0.13. For all reconstructions, non-calibrated IDIFs gave poorer results (>61+/-34% higher slopes) compared with calibrated IDIFs. The results of this study indicate that the use of IDIFs, extracted from OP-OSEM or PVC OP-OSEM images, is feasible for dynamic HRRT data, thereby obviating the need for online arterial sampling.

Comparison of plasma input and reference tissue models for analysing [(11)C]flumazenil studies.

A single-tissue compartment model with plasma input is the established method for analysing [(11)C]flumazenil ([(11)C]FMZ) studies. However, arterial cannulation and measurement of metabolites are time-consuming. Therefore, a reference tissue approach is appealing, but this approach has not been fully validated for [(11)C]FMZ. Dynamic [(11)C]FMZ positron emission tomography scans with arterial blood sampling were performed in nine drug-free depressive patients and eight healthy subjects. Regions of interest were defined on co-registered magnetic resonance imaging scans and projected onto dynamic [(11)C]FMZ images. Using a Hill-type metabolite function, single (1T) and reversible two-tissue (2T) compartmental models were compared. Simplified reference tissue model (SRTM) and full reference tissue model (FRTM) were investigated using both pons and (centrum semiovale) white matter as reference tissue. The 2T model provided the best fit in 59% of cases. Two-tissue V(T) values were on average 1.6% higher than 1T V(T) values. Owing to the higher rejection rate of 2T fits (7.3%), the 1T model was selected as plasma input method of choice. SRTM was superior to FRTM, irrespective whether pons or white matter was used as reference tissue. BP(ND) values obtained with SRTM correlated strongly with 1T V(T) (r=0.998 and 0.995 for pons and white matter, respectively). Use of white matter as reference tissue resulted in 5.5% rejected fits, primarily in areas with intermediate receptor density. No fits were rejected using pons as reference tissue. Pons produced 23% higher BP(ND) values than white matter. In conclusion, for most clinical studies, SRTM with pons as reference tissue can be used for quantifying [(11)C]FMZ binding.

Partial volume corrected image derived input functions for dynamic PET brain studies: methodology and validation for [11C]flumazenil.

Extraction of arterial input functions from dynamic brain scans may obviate the need for arterial sampling and would increase the clinical applicability of quantitative PET studies. The aim of the present study was to evaluate applicability and accuracy of image derived input functions (IDIFs) following reconstruction based partial volume correction (PVC). Settings for the PVC ordered subset expectation maximization (PVC-OSEM) reconstruction algorithm were varied. In addition, different methods for defining arterial regions of interest (ROI) in order to extract IDIFs were evaluated. [(11)C]flumazenil data of 10 subjects were used in the present study. Results obtained with IDIFs were compared with those using standard on-line measured arterial input functions. These included areas under the curve (AUC) for peak (1-2 min) and tail (2-60 min), volume of distribution (V(T)) obtained using Logan analysis, and V(T) and K(1) obtained with a basis function implementation of a single tissue compartment model. Best results were obtained with PVC-OSEM using 4 iterations and 16 subsets. Based on (11)C point source measurements, a 4.5 mm FWHM (full width at half maximum) resolution kernel was used to correct for partial volume effects. A ROI consisting of the four hottest pixels per plane (over the carotid arteries) was the best method to extract IDIFs. Excellent peak AUC ratios (0.99+/-0.09) between IDIF and blood sampler input function (BSIF) were found. Furthermore, extracted IDIFs provided V(T) and K(1) values that were very similar to those obtained using BSIFs. The proposed method appears to be suitable for analysing [(11)C]flumazenil data without the need for online arterial sampling.