EFOMP's protocol quality controls in PET/CT and PET/MR.

This article presents the protocol on Quality Controls in PET/CT and PET/MRI published online in May 2022 by the European Federation of Organisations for Medical Physics (EFOMP), which was developed by the Working group for PET/CT and PET/MRI Quality Control (QC) protocol. The main objective of this protocol was to comprehensively provide simple and practical procedures that may be integrated into clinical practice to identify changes in the PET/CT/MRI system's performance and avoid short- and long-term quality deterioration. The protocol describes the quality control procedures on radionuclide calibrators, weighing scales, PET, CT and MRI systems using selected and measurable parameters that are directly linked to clinical images quality. It helps to detect problems before they can impact clinical studies in terms of safety, image quality, quantification accuracy and patient radiation dose. CT and MRI QCs are described only in the context of their use for PET (attenuation correction and anatomical localization) imaging. Detailed step-by-step instructions have been provided, limiting any misinterpretations or interpersonal variations as much as possible. This paper presents the main characteristics of the protocol illustrated together with a brief summary of the content of each chapter. A regular QC based on the proposed protocol would guarantee that PET/CT and PET/MRI systems operate under optimal conditions, resulting in the best performance for routine clinical tasks.

Prognostic Value of MR Imaging Texture Analysis in Brain Non-Small Cell Lung Cancer Oligo-Metastases Undergoing Stereotactic Irradiation.

UNLABELLED: BACKGROUND : Stereotactic irradiation is widely used in brain oligo-metastases treatment. The aim of this study is to evaluate the prognostic value of magnetic resonance imaging (MRI) texture analysis (TA) of brain metastases (BM) of non-small cell lung cancer (NSCLC). MATERIALS AND METHODS : This study included thirty-eight consecutive patients undergoing stereotactic irradiation, that is, stereotactic fractionated radiotherapy (SRT) or radiosurgery (SRS), from January 2011 to December 2014 for 1-2 brain BM from NSCLC. Whole-brain radiotherapy (WBRT) was not delivered. The diagnostic MRI DICOM (Digital Imaging and Communications in Medicine) images were collected and analyzed with a homemade ImageJ macro, and typical TA parameters (mean, standard deviation, skewness, kurtosis, entropy, and uniformity) were evaluated for: brain progression-free survival; modality of brain metastatic progression (local progression or/and new metastases); and overall survival, after SRT/SRS. RESULTS: After SRT/SRS 14 patients (36.8%) experienced recurrence in the brain, with a recurrence in the irradiated site (five patients, 13.2%), new metastases (11 patients, 28.9%), local recurrence and new metastases (two patients, 5.25%). Nineteen patients (50%) died of tumor progression or other causes. Entropy and uniformity were significantly associated with local progression, whereas kurtosis was significantly associated with both local progression and new brain metastases. CONCLUSIONS : These results appear promising, since the knowledge of factors correlated with the modality of brain progression after stereotactic irradiation of brain oligo-metastatic foci of NSCLC might help in driving the best treatment in these patients (association of SRT/SRS with WBRT? Increase of SRT/SRS dose?). Our preliminary data needs confirmation in large patient series.

Cerebral metabolic rate of glucose quantification with the aortic image-derived input function and Patlak method: numerical and patient data evaluation.

PURPOSE: Quantitative maps of cerebral metabolic rate of glucose (CMRGlu) from fluorine-18 fluorodeoxyglucose-PET are useful in brain studies, but are challenging to acquire because of technical constraints, which hinder their use in clinical routine. Aortic image-derived input functions (IDIFs) combined with Sokoloff's method were proposed as a suitable solution. However, Sokoloff's method requires the use of standard kinetic constants, which may produce biased estimates. Patlak's method would be more appropriate, but concern can arise when used with an aortic IDIF from unavailability of a complete brain curve acquired starting from injection. The aim of this study was to develop a CMRGlu quantification technique that combines Patlak's method with aortic IDIFs in a clinical setting. MATERIALS AND METHODS: A simple acquisition protocol for aortic IDIF measurement was developed and applied on a sample of patients with different degrees of hypometabolism (one healthy control, four patients with a neurodegenerative condition, and one coma patient). CMRGlu estimates in vivo were obtained with both the Sokoloff method and the Patlak method. Computer simulations were performed to assess the causes of bias affecting Sokoloff and Patlak estimates and interpret the results obtained in patients. RESULTS: Simulations showed that Sokoloff's method is less stable than Patlak's method as the extent of bias changed across different physiological states, potentially leading to misinterpretation of clinical data. In clinical patients, Sokoloff and Patlak estimates were correlated on the whole, but deviations emerged for critical physiological states. CONCLUSION: CMRGlu quantification with the Patlak method and aortic IDIF is feasible, easy to implement in clinical practice, and superior to Sokoloff's method from a personalized medicine perspective.

(18)F-FDG PET/CT quantification in head and neck squamous cell cancer: principles, technical issues and clinical applications.

(18)F-FDG PET/CT plays a crucial role in the diagnosis and management of patients with head and neck squamous cell cancer (HNSCC). The major clinical applications of this method include diagnosing an unknown primary tumour, identifying regional lymph node involvement and distant metastases, and providing prognostic information. (18)F-FDG PET/CT is also used for precise delineation of the tumour volume for radiation therapy planning and dose painting, and for treatment response monitoring, by detecting residual or recurrent disease. Most of these applications would benefit from a quantitative approach to the disease, but the quantitative capability of (18)F-FDG PET/CT is still underused in HNSCC. Innovations in PET/CT technology promise to overcome the issues that until now have hindered the employment of dynamic procedures in clinical practice and have limited "quantification" to the evaluation of standardized uptake values (SUV), de facto a semiquantitative parameter, the limits of which are well known to the nuclear medicine community. In this paper the principles of quantitative imaging and the related technical issues are reviewed so that professionals involved in HNSCC management can reflect on the advantages of "true" quantification. A discussion is then presented on how semiquantitative information is currently used in clinical (18)F-FDG PET/CT applications in HNSCC, by discussing the improvements that could be obtained with more advanced and "personalized" quantification techniques.

Surface imaging, portal imaging, and skin marker set-up vs. CBCT for radiotherapy of the thorax and pelvis.

AIM: The aim of this study was to compare surface imaging, portal imaging, and skin marker set-up in radiotherapy of thoracic and pelvic regions, using cone beam computed tomography (CBCT) data as the gold standard. PATIENTS AND METHODS: Twenty patients were included in this study. CBCT, surface acquisition (SA), and two orthogonal portal images (PI) were acquired during the first four treatment sessions. Patient set-up corrections, obtained by registering the planning CT with CBCT, were used as the gold standard. Registration results of the PI and SA were evaluated and compared with those obtained with CBCT. The advantage derived from using SA or PI verification systems over a skin marker set-up was also quantified. RESULTS: A statistically significant difference between PI and SA (in favour of PI) was observed in seven patients undergoing treatment of the pelvic region and in two patients undergoing treatment of the thoracic region. The use of SA or PI, compared with a skin marker set-up, improved patient positioning in 50% and 57% of the thoracic fractions, respectively. For pelvic fractions, the use of PI was beneficial in 73% of the cases, while the use of SA was beneficial in only 45%. Patient positioning worsened with SA, particularly along longitudinal and vertical directions. CONCLUSION: PI yielded more accurate registration results than SA for both pelvic and thoracic fractions. Compared with the skin marker set-up, PI performances were superior to SA for pelvic fractions while comparable results were obtained for thoracic fractions.

A PPAR-gamma agonist attenuates pulmonary injury induced by irradiation in a murine model.

PURPOSE/OBJECTIVE(S): Due to its anti-inflammatory, antifibrotic and antineoplastic properties, the PPAR-γ agonist rosiglitazone is of interest in the prevention and therapy of radiation-induced pulmonary injury. We evaluated the radioprotective effects of rosiglitazone in a murine model of pulmonary damage to determine whether radioprotection was selective for normal and tumor tissues. METHODS: Lungs in C57BL/6J mice were irradiated (19 Gy) with or without rosiglitazone (RGZ, 5mg/kg/day for 16 weeks, oral gavage). Computed tomography (CT) was performed and Hounsfield Units (HU) were determined during the observation period. Histological analysis and evaluation of fibrosis/inflammatory markers by western blot were performed at 16 weeks. A549 tumor-bearing CD1 mice were irradiated (16 Gy) with or without RGZ, and tumor volumes were measured at 35 days. RESULTS: Rosiglitazone reduced radiologic and histologic signs of fibrosis, inflammatory infiltrate, alterations to alveolar structures, and HU lung density that was increased due to irradiation. RGZ treatment also significantly decreased Col1, NF-kB and TGF-ß expression and increased Bcl-2 protein expression compared to the irradiation group and reduced A549 clonogenic survival and xenograft tumor growth. CONCLUSIONS: Rosiglitazone exerted a protective effect on normal tissues in radiation-induced pulmonary injury, while irradiated lung cancer cells were not protected in vivo and in vitro. Thus, rosiglitazone could be proposed as a radioprotective agent in the treatment of lung cancer.

¹²5I-radiolabeled morpholine-containing arginine-glycine-aspartate (RGD) ligand of αvß3 integrin as a molecular imaging probe for angiogenesis.

In this paper, using a hybrid small-animal Micro SPECT/CT imaging system, we report that a new (125)I-Cilengitide-like RGD-cyclopentapeptide, containing d-morpholine-3-carboxylic acid, interacts in vivo with α(v)ß(3) integrin expressed by melanoma cells. Images clearly show that the (125)I-compound has the capacity to monitor the growth of a melanoma xenograft. Indeed, retention of the labeled ligand in the tumor mass has a good tumor/background ratio, and a significant reduction of its uptake was observed after injection of unlabeled ligand. These results suggest that the use of (125)I-labeled morpholine-based RGD-cyclopentapeptides targeting α(v)ß(3) positive tumors may play a role in future therapeutic strategies.

Interaction of caudate dopamine depletion and brain metabolic changes with cognitive dysfunction in early Parkinson's disease.

Damage to nonmotor dopamine (DA)-mediated frontostriatal circuits has been proposed as the main pathophysiological basis of cognitive dysfunction in Parkinson's disease (PD). In the present study, 18 early nondemented drug naive PD patients were investigated, by dual-tracer N-ω-fluoropropyl-2ß-carbomethoxy-3ß-4-[123I]iodophenyl-nortropane ([123I]FP-CIT) single-photon emission computed tomography (SPECT)/[18F] fluoro-deoxyglucose (FDG) positron emission tomography (PET) imaging, to test whether an early and not yet treatment-modulated relation exists between cognitive functions, caudate nucleus (CN) DA impairment and brain metabolism (CMRglc) in associative frontostriatal circuits. Verbal fluency performance correlated with DA impairment in CN, and with CMRglc in dorsolateral prefrontal cortex (DLPFC) and anterior cingulate cortex (ACC). Further, CMRglc in orbitofrontal cortex, DLPFC, and ACC was shown to be early modulated by the level of DA impairment in CN. The present study demonstrates in vivo the early functional disruption of nonmotor frontostriatal circuits in PD. The effect of CN DA impairment on DLPFC and ACC metabolism is proposed as a possible early pathophysiological and functional substrate for executive dysfunction in PD.

Brain metabolic correlates of dopaminergic degeneration in de novo idiopathic Parkinson's disease.

PURPOSE: The aim of the present study was to evaluate the reciprocal relationships between motor impairment, dopaminergic dysfunction, and cerebral metabolism (rCMRglc) in de novo Parkinson's disease (PD) patients. METHODS: Twenty-six de novo untreated PD patients were scanned with (123)I-FP-CIT SPECT and (18)F-FDG PET. The dopaminergic impairment was measured with putaminal (123)I-FP-CIT binding potential (BP), estimated with two different techniques: an iterative reconstruction algorithm (BP(OSEM)) and the least-squares (LS) method (BP(LS)). Statistical parametric mapping (SPM) multiple regression analyses were performed to determine the specific brain regions in which UPDRS III scores and putaminal BP values correlated with rCMRglc. RESULTS: The SPM results showed a negative correlation between UPDRS III and rCMRglc in premotor cortex, and a positive correlation between BP(OSEM) and rCMRglc in premotor and dorsolateral prefrontal cortex, not surviving at multiple comparison correction. Instead, there was a positive significant correlation between putaminal BP(LS) and rCMRglc in premotor, dorsolateral prefrontal, anterior prefrontal, and orbitofrontal cortex (p < 0.05, corrected for multiple comparison). CONCLUSIONS: Putaminal BP(LS) is an efficient parameter for exploring the correlations between PD severity and rCMRglc cortical changes. The correlation between dopaminergic degeneration and rCMRglc in several prefrontal regions likely represents the cortical functional correlate of the dysfunction in the motor basal ganglia-cortical circuit in PD. This finding suggests focusing on the metabolic course of these areas to follow PD progression and to analyze treatment effects.

Evaluation of a method for activity estimation in Sm-153 EDTMP imaging.

Absolute activity evaluation is fundamental for internal radionuclide dosimetry when patient-specific therapy optimization is wanted. Often, quantification is attempted with 3D SPECT image based (IB) methods, but the true concentration values can be underestimated due to the partial volume effect (PVE). This is especially true when small diffuse lesions are present. In this paper, we describe a 3D region of interest (ROI) based quantification method (LS-ROI), which estimates the ROI concentration values directly from the projection data acquired in the tomographic scan once ROIs have been segmented on a CT and/or a SPECT image. The method, which has inherent PVE correction capabilities, was applied both on simulated and on real phantom data. Simulations reflected the case of a patient with bone metastases treated with 153Sm-EDTMP: Both the activity in the metastases and the total retention in the skeleton were evaluated. Thirty noisy data sets were produced in order to evaluate the accuracy and precision of the method. The effect of region segmentation errors on estimated concentrations was thoroughly investigated. Real data were acquired on a NEMA phantom, where a cylindrical central region (283 cm3) simulated the bone and two spheres (10.3 and 25.5 cm3) simulated the metastases. The results obtained with the LS-ROI method were compared with those of a conventional 3D IB method and those of a quantitative conjugate view approach derived from LS-ROI and applied to the anterior and posterior views acquired in the tomographic scan (LS-ROI anterior-posterior: LS-ROI-AP). Simulations showed that when the geometry of regions is known, the LS-ROI method recovered the simulated concentration values within 20%, while the IB method underestimated the concentration in high activity small lesions by as much as 49%. Segmentation errors, up to 44% of the true region volume, produced a higher variation in LS-ROI estimates than in IB ones; however, the overall bias of the LS-ROI estimates (< or = 25%) remained lower than that of IB estimates. In the case of the evaluation of the total retention in the skeleton, the LS-ROI method recovered the simulated value within 2%, while IB underestimated it up to 13%. In all the cases, the LS-ROI-AP method showed an accuracy comparable with that of the LS-ROI one, and a worse precision just because of the lower number of counts used in the analysis. However, a worsening of LS-ROI-AP performances was demonstrated in the case of strong overlap of regions: In this case, a bias of up to 40% was observed. The results obtained on real phantom data confirmed the simulation results: The IB method underestimated activity up to 47% in the smallest sphere, while the bias was reduced to 13% with LS-ROI and LS-ROI-AP estimates. The good quantification capabilities of the LS-ROI method can be useful for absolute activity quantification in the case of small active diffused lesions and constitute the basis for the development of an accurate patient-specific planning strategy in internal radionuclide treatments, provided there is a reliable segmentation of lesions.

Clinical correlation of the binding potential with 123I-FP-CIT in de novo idiopathic Parkinson's disease patients.

PURPOSE: The aim of this study was to evaluate the accuracy of different single-photon emission computed tomography (SPECT) reconstruction techniques in measuring striatal N-omega-fluoropropyl-2beta-carbomethoxy-3beta-4-[(123)I]iodophenyl-nortropane ((123)I-FP-CIT) binding in de novo Parkinson's disease (PD) patients, in order to find a correlation with clinical scales of disease severity in the initial phases of disease. METHODS: Thirty-six de novo PD patients underwent (123)I-FP-CIT SPECT and MRI scan. SPECT data were reconstructed with filtered back projection (FBP), with an iterative algorithm (ordered subset expected maximization, OSEM) and with a method previously developed in our institution, called least-squares (LS) method. The ratio of specific to non-specific striatal (123)I-FP-CIT binding (binding potential, BP) was used as the outcome measure with all the reconstruction methods (BP(FBP), BP(OSEM), BP(LS)). RESULTS: The range of values of striatal BP(LS) was significantly greater than BP(FBP) and BP(OSEM). For all striatal regions, estimates of BP(FBP) correlated well with BP(OSEM) (r = 0.84) and with BP(LS) (r = 0.64); BP(OSEM) correlated significantly with BP(LS) (r = 0.76). A good correlation was found between putaminal BP(LS) and Hoen and Yahr, Unified PD Rating Scale (UPDRS) and lateralized UPDRS motor scores (r = -0.46, r = -0.42, r = -0.39, respectively). Neither putaminal BP(FBP) nor putaminal BP(OSEM) correlated with any of these motor scores. CONCLUSIONS: In de novo PD patients, (123)I-FP-CIT BP values derived from FBP and OSEM reconstruction techniques do not permit to differentiate PD severity. The LS method instead finds a correlation between striatal BP and disease severity scores. The results of this study support the use of (123)I-FP-CIT BP values estimated with the LS method as a biomarker of PD severity.

A direct ROI quantification method for inherent PVE correction: accuracy assessment in striatal SPECT measurements.

PURPOSE: The clinical potential of striatal imaging with dopamine transporter (DAT) SPECT tracers is hampered by the limited capability to recover activity concentration ratios due to partial volume effects (PVE). We evaluated the accuracy of a least squares method that allows retrieval of activity in regions of interest directly from projections (LS-ROI). METHODS: An Alderson striatal phantom was filled with striatal to background ratios of 6:1, 9:1 and 28:1; the striatal and background ROIs were drawn on a coregistered X-ray CT of the phantom. The activity ratios of these ROIs were derived both with the LS-ROI method and with conventional SPECT EM reconstruction (EM-SPECT). Moreover, the two methods were compared in seven patients with motor symptoms who were examined with N-3-fluoropropyl-2-beta-carboxymethoxy-3-beta-(4-iodophenyl) (FP-CIT) SPECT, calculating the binding potential (BP). RESULTS: In the phantom study, the activity ratios obtained with EM-SPECT were 3.5, 5.3 and 17.0, respectively, whereas the LS-ROI method resulted in ratios of 6.2, 9.0 and 27.3, respectively. With the LS-ROI method, the BP in the seven patients was approximately 60% higher than with EM-SPECT; a linear correlation between the LS-ROI and the EM estimates was found (r=0.98, p=0.03). CONCLUSION: The LS-ROI PVE correction capability is mainly due to the fact that the ill-conditioning of the LS-ROI approach is lower than that of the EM-SPECT one. The LS-ROI seems to be feasible and accurate in the examination of the dopaminergic system. This approach can be fruitful in monitoring of disease progression and in clinical trials of dopaminergic drugs.

Kinetic parameter estimation from renal measurements with a three-headed SPECT system: a simulation study.

We present here a direct least-squares estimation (DLSE) method for the determination of renal kinetic parameters from sequences of very fast acquisitions performed with a three-headed single photon emission computed tomography (SPECT) system. A simple linear model for the behavior of the radiopharmaceutical, as well as a spatial model for its spatial distribution are defined. The model enables one to estimate the kinetic parameters directly from the projections, once the plasma concentration function is known. A new technique for the accurate reconstruction of time-radioactivity curves based on the direct reconstruction of the region-of-interest contents from a series of data from three-projections is presented. The technique is used to determine the plasma concentration function with a sub-second time resolution. The spatially-variant geometrical response is also included in the model to compensate for the spatial resolution of the SPECT system. Results obtained from simulations are presented. Basic spatial and time features of the simulations are derived from a patient study. Noise and segmentation errors are also simulated. The DLSE method is compared with the conventional one of deriving kinetic parameters from the time series of reconstructed images. The standard deviation of results given by DLSE is less than 2%, whereas with the conventional method it is between 5% and 6%. Within the limit of statistical fluctuations, DLSE results are unbiased whereas those of the conventional method are overestimated by 24%.