Pitfalls and Limitations of PET/CT in Brain Imaging Salmon, Eric, MD, PhD; Bernard Ir, Claire, ME; Hustinx, Roland, MD, PhD
Seminars in nuclear medicine,
11/2015, Volume:
45, Issue:
6
Journal Article, Web Resource
Peer reviewed
Neurologic applications were at the forefront of PET imaging when the technique was developed in the mid-1970s. Although oncologic indications have become prominent in terms of number of studies ...performed worldwide, neurology remains a major field in which functional imaging provides unique information, both for clinical and research purposes. The evaluation of glucose metabolism using FDG remains the most frequent exploration, but in recent years, alternative radiotracers have been developed, including fluorinated amino acid analogues for primary brain tumor imaging and fluorinated compounds for assessing the amyloid deposits in patients with suspected Alzheimer disease. As the brain is enclosed in the skull, which presents fixed landmarks, it is relatively easy to coregister images obtained with various cross-sectional imaging methods, either functional or anatomical, with a relatively high accuracy and robustness. Nevertheless, PET in neurology has fully benefited from the advent of hybrid imaging. Attenuation and scatter correction is now much faster and equally accurate, using CT as compared with the traditional transmission scan using an external radioactive source. The perfect coregistration with the CT data, which is now systematically performed, also provides its own set of valuable information, for instance regarding cerebral atrophy. However, hybrid imaging in neurology comes with pitfalls and limitations, in addition to those that are well known, for example, blood glucose levels or psychotropic drugs that greatly affect the physiological FDG uptake. Movements of the patientʼs head, either during the PET acquisition or between the PET and the CT acquisitions will generate artifacts that may be very subtle yet lead to erroneous interpretation of the study. Similarly, quantitative analysis, such as voxel-based analyses, may prove very helpful in improving the diagnostic accuracy and the reproducibility of the reading, but a wide variety of artifacts may also be introduced, and should therefore be identified and corrected.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Introduction
With
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F-FDG PET/CT, tumor uptake intensity and heterogeneity have been associated with outcome in several cancers. This study aimed at investigating whether
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F-FDG uptake intensity, ...volume or heterogeneity could predict the outcome in patients with non-small cell lung cancers (NSCLC) treated by stereotactic body radiation therapy (SBRT).
Methods
Sixty-three patients with NSCLC treated by SBRT underwent a
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F-FDG PET/CT before treatment. Maximum and mean standard uptake value (SUVmax and SUVmean), metabolic tumoral volume (MTV), total lesion glycolysis (TLG), as well as 13 global, local and regional textural features were analysed. The predictive value of these parameters, along with clinical features, was assessed using univariate and multivariate analysis for overall survival (OS), disease-specific survival (DSS) and disease-free survival (DFS). Cutoff values were obtained using logistic regression analysis, and survivals were compared using Kaplan-Meier analysis.
Results
The median follow-up period was 27.1 months for the entire cohort and 32.1 months for the surviving patients. At the end of the study, 25 patients had local and/or distant recurrence including 12 who died because of the cancer progression. None of the clinical variables was predictive of the outcome, except age, which was associated with DFS (HR 1.1,
P
= 0.002). None of the
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F-FDG PET/CT or clinical parameters, except gender, were associated with OS. The univariate analysis showed that only dissimilarity (D) was associated with DSS (HR = 0.822,
P
= 0.037), and that several metabolic measurements were associated with DFS. In multivariate analysis, only dissimilarity was significantly associated with DSS (HR = 0.822,
P
= 0.037) and with DFS (HR = 0.834,
P
< 0.01).
Conclusion
The textural feature dissimilarity measured on the baseline
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F-FDG PET/CT appears to be a strong independent predictor of the outcome in patients with NSCLC treated by SBRT. This may help selecting patients who may benefit from closer monitoring and therapeutic optimization.
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DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, SIK, UILJ, UKNU, UL, UM, UPUK, VKSCE, VSZLJ, ZAGLJ
The differentiation of the vegetative or unresponsive wakefulness syndrome (VS/UWS) from the minimally conscious state (MCS) is an important clinical issue. The cerebral metabolic rate of glucose ...(CMRglc) declines when consciousness is lost, and may reveal the residual cognitive function of these patients. However, no quantitative comparisons of cerebral glucose metabolism in VS/UWS and MCS have yet been reported. We calculated the regional and whole-brain CMRglc of 41 patients in the states of VS/UWS (n=14), MCS (n=21) or emergence from MCS (EMCS, n=6), and healthy volunteers (n=29). Global cortical CMRglc in VS/UWS and MCS averaged 42% and 55% of normal, respectively. Differences between VS/UWS and MCS were most pronounced in the frontoparietal cortex, at 42% and 60% of normal. In brainstem and thalamus, metabolism declined equally in the two conditions. In EMCS, metabolic rates were indistinguishable from those of MCS. Ordinal logistic regression predicted that patients are likely to emerge into MCS at CMRglc above 45% of normal. Receiver-operating characteristics showed that patients in MCS and VS/UWS can be differentiated with 82% accuracy, based on cortical metabolism. Together these results reveal a significant correlation between whole-brain energy metabolism and level of consciousness, suggesting that quantitative values of CMRglc reveal consciousness in severely brain-injured patients.
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NUK, OILJ, SAZU, UKNU, UL, UM, UPUK
Advanced ovarian cancer is the most lethal gynecological cancer, with a high rate of chemoresistance and relapse. Photodynamic therapy offers new prospects for ovarian cancer treatment, but current ...photosensitizers lack tumor specificity, resulting in low efficacy and significant side-effects. In the present work, the clinically approved photosensitizer verteporfin was encapsulated within nanostructured lipid carriers (NLC) for targeted photodynamic therapy of ovarian cancer. Cellular uptake and phototoxicity of free verteporfin and NLC-verteporfin were studied in vitro in human ovarian cancer cell lines cultured in 2D and 3D-spheroids, and biodistribution and photodynamic therapy were evaluated in vivo in mice. Both molecules were internalized in ovarian cancer cells and strongly inhibited tumor cells viability when exposed to laser light only. In vivo biodistribution and pharmacokinetic studies evidenced a long circulation time of NLC associated with efficient tumor uptake. Administration of 2 mg.kg
free verteporfin induced severe phototoxic adverse effects leading to the death of 5 out of 8 mice. In contrast, laser light exposure of tumors after intravenous administration of NLC-verteporfin (8 mg.kg
) significantly inhibited tumor growth without visible toxicity. NLC-verteporfin thus led to efficient verteporfin vectorization to the tumor site and protection from side-effects, providing promising therapeutic prospects for photodynamic therapy of cancer.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Background
2-
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Ffluoro-2-deoxy-D-glucose (
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FFDG) positron emission tomography combined with low-dose computed tomography (PET/CT) can be used at diagnosis to identify myeloma-defining events and ...also provides prognostic factors. The aim of this study was to assess the prognostic significance of baseline
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FFDG PET/CT visual IMPeTUs (Italian myeloma criteria for PET Use)-based parameters and/or total metabolic tumor volume (TMTV) in a single-center population of patients with newly diagnosed multiple myeloma (NDMM) eligible for transplantation.
Methods
Patients with MM who underwent a baseline
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FFDG PET/CT were retrospectively selected from a large internal database of the University Hospital of Liege (Liege, Belgium). Initially, all PET/CT images were visually analyzed using IMPeTUs criteria, followed by delineation of TMTV using a semi-automatic lesion delineation workflow, including
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FFDG-positive MM focal lesions (FL) with an absolute SUV threshold set at 4.0. In a first step, to ensure PET/CT scans accurate reporting, the agreement between two nuclear medicine physicians with distinct experience was assessed. In the second step, univariable and multivariable analyses were conducted to determine the prognostic significance of
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FFDG PET/CT parameters on progression free survival (PFS) and overall survival (OS), respectively.
Results
A total of 40 patients with NDMM were included in the study. The observers agreement in the analysis 18FFDG PET/CT images was substantial for the presence of spine FL, extra spine FL, at least one fracture and paramedullary disease (Cohen’s kappa 0.79, 0.87, 0.75 and 0.64, respectively). For the presence of skull FL and extramedullary disease the agreement was moderate (Cohen’s kappa 0.56 and 0.53, respectively). Among
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FFDG PET/CT parameters, a high number of delineated volumes of interest (VOI) using the SUV4.0 threshold was the only independent prognostic factor associated with PFS HR (95% CI): 1.03 (1.004–1.05),
P
= 0.019 while a high number of FL (
n
> 10; F group 4) was the only independent prognostic factor associated with OS HR (95% CI): 19.10 (1.90–191.95),
P
= 0.01.
Conclusion
Our work confirms the reproducibility IMPeTUs criteria. Furthermore, it demonstrates that a high number of FL (
n
> 10; IMPeTUs F group 4), reflecting a high
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FFDG-avid tumor burden, is an independent prognostic factor for OS. The prognostic value of the TMTV delineated using a SUV4.0 threshold was not significant. Nevertheless, the count of delineated
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FFDG-avid lesions VOI using a SUV4.0 threshold was an independent prognostic factor for PFS.
High Nature Value (HNV) farmlands currently retain most of the biodiversity associated with agricultural landscapes in Europe. In a time of globalized food systems, the social-ecological conditions ...to maintain these low-intensity and thus less productive HNV farming systems are difficult to meet. Halting the loss of HNV farmland requires fostering the socioeconomic viability of HNV farming systems that is compatible with social, cultural, and ecological values. Pursuing such viability calls for tailored actions to steer the development of HNV farming systems based on the strength of their local assets. Such a transformational learning process involves changing the territorial dynamic towards better integration of biodiversity at several levels of management (from farm to territorial level). Based on the description and analysis of ten HNV territories distributed across Europe, we explore how HNV innovation brokers can strategically engage with local actors to preserve the environmental characteristics of HNV farmland areas while improving their socioeconomic viability. The aim of this research is to improve the understanding of the range of approaches and strategies of innovation brokers to meet the challenges of HNV farmland conservation. The study analyzes the different innovation processes that took place in each area, concentrating on the engagement phase. Our results demonstrate that HNV farming situations across Europe are quite diverse from an agroecological and socioeconomic point of view. There are distinct conservation challenges and associated risks for each HNV farming context. The need for a strategic approach to HNV conservation at landscape–territory level is discussed. The key role of innovation brokers is highlighted, together with the need for a strategic approach to innovation brokerage, which is explicit in relation to territorial needs and the changes required. We demonstrate the importance of the landscape–territorial vision as an entry point for shaping HNV farming systems towards socially desirable scenarios.
Abstract Sarcoidosis is an inflammatory disease marked by a paradoxical immune status. The anergic state, which results from various immune defects, contrasts with the inflammatory formation of ...granulomas. Sarcoidosis patients may be at risk for opportunistic infections (OIs) and a substantial number of cases have been reported, even in untreated sarcoidosis. It is not clear how OIs in patients with sarcoidosis are different from other groups at risk. In this review, we discuss the most common OIs: mycobacterial infection (including tuberculosis), cryptococcosis, progressive multifocal leukoencephalopathy, and aspergillosis. Unlike peripheral lymphocytopenia, corticosteroids are a major risk factor for OIs but the occurrence of Ols in untreated patients suggests more complex predisposing mechanisms. Opportunistic infections presenting with extrapulmonary features are often misdiagnosed as new localizations of sarcoidosis. Aspergillomas mostly develop on fibrocystic lungs. Overall, physicians should be aware of the possible occurrence of OIs during sarcoidosis, even in untreated patients.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Background
Four state-of-the-art single-photon emission computed tomography-computed tomography (SPECT-CT) systems, namely Philips Brightview, General Electric Discovery NM/CT 670 and Infinia Hawkeye ...4, and Siemens Symbia T6, were investigated in terms of accuracy of attenuation and scatter correction, contrast recovery for small hot and cold structures, and quantitative capabilities when using their dedicated three-dimensional iterative reconstruction with attenuation and scatter corrections and resolution recovery.
Methods
The National Electrical Manufacturers Association (NEMA) NU-2 1994 phantom with cold air, water, and Teflon inserts, and a homemade contrast phantom with hot and cold rods were filled with
99m
Tc and scanned. The acquisition parameters were chosen to provide adequate linear and angular sampling and high count statistics. The data were reconstructed using Philips Astonish, General Electric Evolution for Bone, or Siemens Flash3D, eight subsets, and a varying number of iterations. A procedure similar to the one used in positron emission tomography (PET) allowed us to obtain the factor to convert counts per pixel into activity per unit volume.
Results
Edge and oscillation artifacts were observed with all phantoms and all systems. At 30 iterations, the residual fraction in the inserts of the NEMA phantom fell below 3.5%. Contrast recovery increased with the number of iterations but became almost saturated at 24 iterations onwards. In the uniform part of the NEMA and contrast phantoms, a quantification error below 10% was achieved.
Conclusions
In objects whose dimensions exceeded the SPECT spatial resolution by several times, quantification seemed to be feasible within 10% error limits. A partial volume effect correction strategy remains necessary for the smallest structures. The reconstruction artifacts nevertheless remain a handicap on the road towards accurate quantification in SPECT and should be the focus of further works in reconstruction tomography.
A novel, inexpensive and versatile ionic-liquid-based catch and release mass spectrometry tag (I-Tag) that facilitates substrate purification, fast, robust and sensitive enzymatic reaction monitoring ...and quantitative kinetic analysis has been developed. The applicability of the system has been demonstrated in an enzymatic assay with β-1,4-galactosyltransferase.
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