Robin de Nijs

In Vivo Proton MR Spectroscopy of the Breast Using the Total Choline Peak Integral as a Marker of Malignancy

OBJECTIVE The purpose of our study was to use the total choline-containing compound (tCho) peak integral as a marker of malignancy in breast MR spectroscopy (MRS). SUBJECTS AND METHODS Forty-eight single-voxel water- and fat-suppressed 1.5-T MRS measurements were performed in 42 patients, obtaining both absolute tCho peak integral and tCho peak integral normalized for the volume of interest (VOI). Our reference standard was histology for lesions with BI-RADS category 4 and 5 and histology or at least a 2-year follow-up for findings with BI-RADS 2 and 3 and normal glands. Receiver operating characteristic (ROC) analysis, Mann-Whitney U test, and Spearmans rank correlation were used. RESULTS Three of 48 measurements (6%) failed. Of the remaining 45 spectra, 18 nonmalignant tissues showed no tCho peak, eight nonmalignant tissues showed a tCho peak integral from 0.99 to 9.03 arbitrary units (AU), and 19 malignant lesions showed a tCho peak integral from 1.26 to 19.80 AU. The diameter of nonmalignant tissues was 16.9 +/- 7.4 mm; that of malignant lesions was 15.3 +/- 6.9 mm (p = 0.308). At ROC analysis, the optimal threshold was 1.90 AU for absolute tCho peak, with 0.895 (17/19) sensitivity, 0.923 (24/26) specificity, and an AUC (area under the curve) of 0.917 (95% CI, 0.822-1.000); the optimal threshold was 0.85 AU/mL for the normalized tCho peak integral with 0.842 (16/19) sensitivity, 0.885 (23/26) specificity, and an AUC of 0.941 (0.879-1.000) (p = 0.470). A negative correlation (p = 0.011) was found between the VOI and the normalized tCho peak integral of malignant tissues. CONCLUSION Breast MRS using tCho peak integral reaches a high level of diagnostic performance.

Calibration of gamma camera systems for a multicentre European 123I-FP-CIT SPECT normal database

PurposeA joint initiative of the European Association of Nuclear Medicine (EANM) Neuroimaging Committee and EANM Research Ltd. aimed to generate a European database of [123I]FP-CIT single photon emission computed tomography (SPECT) scans of healthy controls. This study describes the characterization and harmonization of the imaging equipment of the institutions involved.Methods123I SPECT images of a striatal phantom filled with striatal to background ratios between 10:1 and 1:1 were acquired on all the gamma cameras with absolute ratios measured from aliquots. The images were reconstructed by a core lab using ordered subset expectation maximization (OSEM) without corrections (NC), with attenuation correction only (AC) and additional scatter and septal penetration correction (ACSC) using the triple energy window method. A quantitative parameter, the simulated specific binding ratio (sSBR), was measured using the “Southampton” methodology that accounts for the partial volume effect and compared against the actual values obtained from the aliquots. Camera-specific recovery coefficients were derived from linear regression and the error of the measurements was evaluated using the coefficient of variation (COV).ResultsThe relationship between measured and actual sSBRs was linear across all systems. Variability was observed between different manufacturers and, to a lesser extent, between cameras of the same type. The NC and AC measurements were found to underestimate systematically the actual sSBRs, while the ACSC measurements resulted in recovery coefficients close to 100% for all cameras (AC range 69–89%, ACSC range 87–116%). The COV improved from 46% (NC) to 32% (AC) and to 14% (ACSC) (p < 0.001).ConclusionA satisfactory linear response was observed across all cameras. Quantitative measurements depend upon the characteristics of the SPECT systems and their calibration is a necessary prerequisite for data pooling. Together with accounting for partial volume, the correction for scatter and septal penetration is essential for accurate quantification.

Proposal for the standardisation of multi-centre trials in nuclear medicine imaging: prerequisites for a European 123I-FP-CIT SPECT database.

PurposeMulti-centre trials are an important part of proving the efficacy of procedures, drugs and interventions. Imaging components in such trials are becoming increasingly common; however, without sufficient control measures the usefulness of these data can be compromised. This paper describes a framework for performing high-quality multi-centre trials with single photon emission computed tomography (SPECT), using a pan-European initiative to acquire a normal control dopamine transporter brain scan database as an example.MethodsA framework to produce high-quality and consistent SPECT imaging data was based on three key areas: quality assurance, the imaging protocol and system characterisation. Quality assurance was important to ensure that the quality of the equipment and local techniques was good and consistently high; system characterisation helped understand and where possible match the performance of the systems involved, whereas the imaging protocol was designed to allow a degree of flexibility to best match the characteristics of each imaging device.ResultsA total of 24 cameras on 15 sites from 8 different manufacturers were evaluated for inclusion in our multi-centre initiative. All results matched the required level of specification and each had their performance characterised. Differences in performance were found between different system types and cameras of the same type. Imaging protocols for each site were modified to match their individual characteristics to produce comparable high-quality SPECT images.ConclusionA framework has been designed to produce high-quality data for multi-centre SPECT studies. This framework has been successfully applied to a pan-European initiative to acquire a healthy control dopamine transporter image database.

Evaluation of the Serotonin Transporter Ligand 123I-ADAM for SPECT Studies on Humans

Imaging serotonin transporters in the living human brain is important in several fields, such as normal psychophysiology, mood disorders, eating disorders, and neurodegenerative disorders. The aim of this study was to compare different kinetic and semiquantitative methods for assessing serotonin transporters using 123I-labeled 2-((2-((dimethylamino)methyl)phenyl)thio)-5-iodophenylamine (ADAM) in humans: an arterial plasma input model, simplified and Logan reference tissue models, and standardized uptake value ratios. Methods: Nine subjects were scanned with dynamic 123I-ADAM SPECT (mean age, 31 y; range, 24–43 y), and metabolite-corrected arterial input was measured. Tissue reference models (simplified reference tissue model, Logan reference tissue model, and ratio method) were validated against the outcome of a 1-tissue-compartment model, and performance with decreasing scan length was evaluated. The specificity of 123I-ADAM binding was investigated in a blocking experiment. Results: Binding estimates from the simplified reference tissue and Logan reference tissue models correlated tightly with full kinetic modeling when based on a 240- or 360-min dynamic acquisition (r = 0.99); however, there were slight underestimations (3%–5%), especially in high-binding regions. Application of the ratio method to data from 200 to 240 min overestimated specific binding (on average, by 10% ± 28%) and correlated only moderately with estimates from the 1-tissue-compartment model (r = 0.94). With an acquisition time of 0–120 min, the Logan model still yielded an acceptable outcome when a fixed clearance rate constant (k2′) from the cerebellum was applied. Intravenously injected citalopram was not associated with a decrease in cerebellar binding. A lipophilic metabolite that did not seem to bind specifically to serotonin transporter was seen in 2 of 7 subjects. Conclusion: Serotonin transporter binding with 123I-ADAM SPECT can be assessed with the Logan model based on a 120-min acquisition when a constant k2′ is applied. This model, because it allows for more accurate and less biased binding estimates and thus reduces the required sample size, is advantageous over the ratio method used in clinical studies so far. A single blocking experiment supported the use of the cerebellum as a reference region.

Improving quantitative dosimetry in (177)Lu-DOTATATE SPECT by energy window-based scatter corrections.

PurposePatient-specific dosimetry of lutetium-177 (177Lu)-DOTATATE treatment in neuroendocrine tumours is important, because uptake differs across patients. Single photon emission computer tomography (SPECT)-based dosimetry requires a conversion factor between the obtained counts and the activity, which depends on the collimator type, the utilized energy windows and the applied scatter correction techniques. In this study, energy window subtraction-based scatter correction methods are compared experimentally and quantitatively. Materials and methods177Lu SPECT images of a phantom with known activity concentration ratio between the uniform background and filled hollow spheres were acquired for three different collimators: low-energy high resolution (LEHR), low-energy general purpose (LEGP) and medium-energy general purpose (MEGP). Counts were collected in several energy windows, and scatter correction was performed by applying different methods such as effective scatter source estimation (ESSE), triple-energy and dual-energy window, double-photopeak window and downscatter correction. The intensity ratio between the spheres and the background was measured and corrected for the partial volume effect and used to compare the performance of the methods. ResultsLow-energy collimators combined with 208 keV energy windows give rise to artefacts. For the 113 keV energy window, large differences were observed in the ratios for the spheres. For MEGP collimators with the ESSE correction technique, the measured ratio was close to the real ratio, and the differences between spheres were small. ConclusionFor quantitative 177Lu imaging MEGP collimators are advised. Both energy peaks can be utilized when the ESSE correction technique is applied. The difference between the calculated and the real ratio is less than 10% for both energy windows.

TSPO Imaging in Glioblastoma Multiforme: A Direct Comparison Between 123I-CLINDE SPECT, 18F-FET PET, and Gadolinium-Enhanced MR Imaging

Here we compare translocator protein (TSPO) imaging using 6-chloro-2-(4′-123I-iodophenyl)-3-(N,N-diethyl)-imidazo[1,2-a]pyridine-3-acetamide SPECT (123I-CLINDE) and amino acid transport imaging using O-(2-18F-fluoroethyl)-l-tyrosine PET (18F-FET) and investigate whether 123I-CLINDE is superior to 18F-FET in predicting progression of glioblastoma multiforme (GBM) at follow-up. Methods: Three patients with World Health Organization grade IV GBM were scanned with 123I-CLINDE SPECT, 18F-FET PET, and gadolinium-enhanced MR imaging. Molecular imaging data were compared with follow-up gadolinium-enhanced MR images or contrast-enhanced CT scans. Results: The percentage overlap between volumes of interest (VOIs) of increased 18F-FET uptake and 123I-CLINDE binding was variable (12%–42%). The percentage overlap of MR imaging baseline VOIs was greater for 18F-FET (79%–93%) than 123I-CLINDE (15%–30%). In contrast, VOIs of increased contrast enhancement at follow-up compared with baseline overlapped to a greater extent with baseline 123I-CLINDE VOIs than 18F-FET VOIs (21% vs. 8% and 72% vs. 55%). Conclusion: Our preliminary results suggest that TSPO brain imaging in GBM may be a useful tool for predicting tumor progression at follow-up and may be less susceptible to changes in blood–brain barrier permeability than 18F-FET. Larger studies are warranted to test the clinical potential of TSPO imaging in GBM, including presurgical planning and radiotherapy.

Validation of a Method for Accurate and Highly Reproducible Quantification of Brain Dopamine Transporter SPECT Studies

In nuclear medicine brain imaging, it is important to delineate regions of interest (ROIs) so that the outcome is both accurate and reproducible. The purpose of this study was to validate a new time-saving algorithm (DATquan) for accurate and reproducible quantification of the striatal dopamine transporter (DAT) with appropriate radioligands and SPECT and without the need for structural brain scanning. Methods: In a reconstructed DAT SPECT image, DATquan automatically calculated the ratio at steady state of specifically bound radioligand to nondisplaceable radioligand in tissue (BPND) within striatal ROIs that were delineated by use of a semiautomatic template-based alignment approach. DATquan was tested with 123I-N-(3-iodoprop-2E-enyl)-2-β-carbomethoxy-3β-(4-methylphenyl) SPECT images from 15 patients. In each image, ROIs were first manually delineated, and then corresponding BPND values were derived by an experienced physician. Afterward, 2 independent novice operators used DATquan to analyze the same 15 images. The resulting DATquan-derived BPND data were compared with the data retrieved by manual delineation to assess the accuracy and reproducibility of DATquan. Also, the operational aspects of DATquan were assessed on the basis of measurements of the mean running time of the algorithm as well as on the basis of quantification of the overlap of the DATquan-delineated ROIs obtained by the 2 operators. Results: The mean algorithm running time was 3 min, and the operators’ striatal ROIs had a mean overlap of more than 82%. DATquan-derived BPND values obtained by the 2 operators showed high agreement (the mean difference was 0.00 [SD, 0.05] in the striatum, 0.02 [SD, 0.26] in the putamen, and 0.03 [SD, 0.43] in the caudate nucleus). The interoperator variability was 2.2% (SD, 1.3%) in the striatum, 11.7% (SD, 9.9%) in the putamen, and 12.9% (SD, 4.0%) in the caudate nucleus. DATquan-derived BPND values showed high agreement with the values manually derived by the experienced delineator. Conclusion: DATquan is a freely available, accurate, and highly reproducible method for quantification of DAT binding in the brain by SPECT. Once implemented in clinics, DATquan will serve as a useful and time-saving tool.

MRI-Guided Region-of-Interest Delineation Is Comparable to Manual Delineation in Dopamine Transporter SPECT Quantification in Patients: A Reproducibility Study

A particularly sensitive step in the quantification of SPECT images of the dopamine transporter (DAT) is a correct delineation of the region of interest (ROI). In this study, we primarily compared the reproducibility of the following different approaches for ROI delineation in SPECT images of the DAT: the use of manual delineation (MD) on high-count striatal slides directly on the SPECT image, ROI delineation based on individual MR images (MRD), and oversized striatal ROIs—that is, the striatal volume of interest (SVI), as described previously. We also assessed the ability of the different approaches to identify striatal pathology in patients with parkinsonism. Methods: Eight patients with highly variable reductions in cerebral DAT availability were SPECT-scanned twice with 123I-labeled N-(3-iodoprop-(2E)-enyl)-2β-carboxymethoxy-3β-(4′-methylphenyl) nortropane bolus infusion setup and once with an MRI scanner. For SPECT/MRI coregistration, we used external fiducial markers visible on both MRI and SPECT. With the MD and MRD methods, the outcome parameters for DAT availability were the binding potentials and the ratio at equilibrium of specifically bound radioligand to nondisplaceable radioligand in tissue (BPND). For the SVI method, the outcome parameter was the specific binding ratio (SBR). Results: No statistically significant difference in striatal BPND intraobserver reproducibility was seen among any of the 3 methods. The intraobserver reproducibility average ± SD for MD was 7.0% ± 4.1%; for MRD, 5.7% ± 5.4%; and for SVI, 6.7% ± 6.0%. Mean intrasubject variability, as determined from the test–retest scans, did not differ with the 3 delineation methods used. The average (±SD) intrasubject variability of striatal BPND was 11.9% ± 10.0% with MD and 14.6% ± 15.3% with MRD. With the SVI method, the intrasubject variability of striatal specific binding ratio was 10.0% ± 10.2%. BPND values obtained with the MD and MRD methods were similar (paired t test, P > 0.4). Conclusion: In patients with reduced striatal DAT binding, the reproducibility of the outcome from ROI MD is comparable to both that obtained by delineation of ROI on individual MR images, followed by coregistration to the SPECT image, and that obtained with the SVI-based approach.

Experimental determination of the weighting factor for the energy window subtraction-based downscatter correction for I-123 in brain SPECT studies

Correction for downscatter in I-123 SPECT can be performed by the subtraction of a secondary energy window from the main window, as in the triple-energy window method. This is potentially noise sensitive. For studies with limited amount of counts (e.g. dynamic studies), a broad subtraction window with identical width is preferred. This secondary window needs to be weighted with a factor higher than one, due to a broad backscatter peak from high-energy photons appearing at 172 keV. Spatial dependency and the numerical value of this weighting factor and the image contrast improvement of this correction were investigated in this study. Energy windows with a width of 32 keV were centered at 159 keV and 200 keV. The weighting factor was measured both with an I-123 point source and in a dopamine transporter brain SPECT study in 10 human subjects (5 healthy subjects and 5 patients) by minimizing the background outside the head. Weighting factors ranged from 1.11 to 1.13 for the point source and from 1.16 to 1.18 for human subjects. Point source measurements revealed no position dependence. After correction, the measured specific binding ratio (image contrast) increased significantly for healthy subjects, typically by more than 20%, while the background counts outside of all subjects were effectively removed. A weighting factor of 1.1-1.2 can be applied in clinical practice. This correction effectively removes downscatter and significantly improves image contrast inside the brain.

[(123)I]FP-CIT ENC-DAT normal database: the impact of the reconstruction and quantification methods.

Background[123I]FP-CIT is a well-established radiotracer for the diagnosis of dopaminergic degenerative disorders. The European Normal Control Database of DaTSCAN (ENC-DAT) of healthy controls has provided age and gender-specific reference values for the [123I]FP-CIT specific binding ratio (SBR) under optimised protocols for image acquisition and processing. Simpler reconstruction methods, however, are in use in many hospitals, often without implementation of attenuation and scatter corrections. This study investigates the impact on the reference values of simpler approaches using two quantifications methods, BRASS and Southampton, and explores the performance of the striatal phantom calibration in their harmonisation.ResultsBRASS and Southampton databases comprising 123 ENC-DAT subjects, from gamma cameras with parallel collimators, were reconstructed using filtered back projection (FBP) and iterative reconstruction OSEM without corrections (IRNC) and compared against the recommended OSEM with corrections for attenuation and scatter and septal penetration (ACSC), before and after applying phantom calibration. Differences between databases were quantified using the percentage difference of their SBR in the dopamine transporter-rich striatum, with their significance determined by the paired t test with Bonferroni correction.Attenuation and scatter losses, measured from the percentage difference between IRNC and ACSC databases, were of the order of 47% for both BRASS and Southampton quantifications. Phantom corrections were able to recover most of these losses, but the SBRs remained significantly lower than the “true” values (p < 0.001). Calibration provided, in fact, “first order” camera-dependent corrections, but could not include “second order” subject-dependent effects, such as septal penetration from extra-cranial activity. As for the ACSC databases, phantom calibration was instrumental in compensating for partial volume losses in BRASS (~67%, p < 0.001), while for the Southampton method, inherently free from them, it brought no significant changes and solely corrected for residual inter-camera variability (−0.2%, p = 0.44).ConclusionsThe ENC-DAT reference values are significantly dependent on the reconstruction and quantification methods and phantom calibration, while reducing the major part of their differences, is unable to fully harmonize them. Clinical use of any normal database, therefore, requires consistency with the processing methodology. Caution must be exercised when comparing data from different centres, recognising that the SBR may represent an “index” rather than a “true” value.