Roland Hustinx

Role of Imaging in the Staging and Response Assessment of Lymphoma: Consensus of the International Conference on Malignant Lymphomas Imaging Working Group

PURPOSE Recent advances in imaging, use of prognostic indices, and molecular profiling techniques have the potential to improve disease characterization and outcomes in lymphoma. International trials are under way to test image-based response–adapted treatment guided by early interim positron emission tomography (PET)–computed tomography (CT). Progress in imaging is influencing trial design and affecting clinical practice. In particular, a five-point scale to grade response using PET-CT, which can be adapted to suit requirements for early- and late-response assessment with good interobserver agreement, is becoming widely used both in practice- and response-adapted trials. A workshop held at the 11th International Conference on Malignant Lymphomas (ICML) in 2011 concluded that revision to current staging and response criteria was timely. METHODS An imaging working group composed of representatives from major international cooperative groups was asked to review the literature, share knowledge about research in progress, and identify key areas for research pertaining to imaging and lymphoma. RESULTS A working paper was circulated for comment and presented at the Fourth International Workshop on PET in Lymphoma in Menton, France, and the 12th ICML in Lugano, Switzerland, to update the International Harmonisation Project guidance regarding PET. Recommendations were made to optimize the use of PET-CT in staging and response assessment of lymphoma, including qualitative and quantitative methods. CONCLUSION This article comprises the consensus reached to update guidance on the use of PET-CT for staging and response assessment for [18F]fluorodeoxyglucose-avid lymphomas in clinical practice and late-phase trials.

Oncological Applications of Positron Emission Tomography with Fluorine-18 Fluorodeoxyglucose

Positron emission tomography (PET) is now primarily used in oncological indication owing to the successful application of fluorine-18 fluorodeoxyglucose (FDG) in an increasing number of clinical indications at different stages of diagnosis, and for staging and follow-up. This review first considers the biological characteristics of FDG and then discusses methodological considerations regarding its use. Clinical indications are considered, and the results achieved in respect of various organs and tumour types are reviewed in depth. The review concludes with a brief consideration of the ways in which clinical PET might be improved.

Intrinsic Brain Activity in Altered States of Consciousness : How Conscious Is the Default Mode of Brain Function?

Spontaneous brain activity has recently received increasing interest in the neuroimaging community. However, the value of resting‐state studies to a better understanding of brain–behavior relationships has been challenged. That altered states of consciousness are a privileged way to study the relationships between spontaneous brain activity and behavior is proposed, and common resting‐state brain activity features observed in various states of altered consciousness are reviewed. Early positron emission tomography studies showed that states of extremely low or high brain activity are often associated with unconsciousness. However, this relationship is not absolute, and the precise link between global brain metabolism and awareness remains yet difficult to assert. In contrast, voxel‐based analyses identified a systematic impairment of associative frontoparieto–cingulate areas in altered states of consciousness, such as sleep, anesthesia, coma, vegetative state, epileptic loss of consciousness, and somnambulism. In parallel, recent functional magnetic resonance imaging studies have identified structured patterns of slow neuronal oscillations in the resting human brain. Similar coherent blood oxygen level–dependent (BOLD) systemwide patterns can also be found, in particular in the default‐mode network, in several states of unconsciousness, such as coma, anesthesia, and slow‐wave sleep. The latter results suggest that slow coherent spontaneous BOLD fluctuations cannot be exclusively a reflection of conscious mental activity, but may reflect default brain connectivity shaping brain areas of most likely interactions in a way that transcends levels of consciousness, and whose functional significance remains largely in the dark.

Positron emission tomography (PET) with 18F-fluorodeoxyglucose (18F-FDG) for the staging of low-grade non-Hodgkin's lymphoma (NHL).

BACKGROUND Although PET has been shown to be highly sensitive in the primary staging of lymphoma, previous studies with small numbers of patients indicated that low-grade NHL may not always be adequately detected by PET. We undertook this study to determine factors influencing the detection of lesions by PET in low-grade NHL and to evaluate the utility of PET in this indication. PATIENTS AND METHODS Forty-two patients underwent conventional staging procedures (clinical examination, oto-rhino-laryngologic examination, computed tomography of the chest, abdomen and pelvis, gastroscopy and bone marrow biopsy as well as whole-body non-attenuation corrected 18F-FDG-PET RESULTS: PET detected 40% more abnormal lymph node areas than conventional staging in follicular lymphoma but was inappropriate for the staging of small lymphocytic lymphoma where it detected less than 58% of abnormal lymph node areas. PET showed more lesions than conventional staging for peripheral (34% more lymph node areas detected) and thoracic lymph node (39% more) areas but not for abdominal or pelvic lymph nodes (26% fewer areas detected). The sensitivity to detect bone marrow infiltration was unacceptably low for PET. In contrast, PET was as effective as standard procedures for the detection of other extranodal localizations, although a few localizations were detected only by PET and a few others only by conventional procedures. CONCLUSIONS PET may contribute to the management of patients with low-grade follicular NHL. For the other low-grade lymphoma subtypes, the role of PET is less evident. Further studies using PET to evaluate the results of treatment or to diagnose disease recurrence are warranted in low-grade follicular NHL.

Imaging of large vessel vasculitis with (18)FDG PET: illusion or reality? A critical review of the literature data

Fluorine-18 fluorodeoxyglucose positron emission tomography (18FDG PET) plays a major role in the management of oncology patients. Owing to the singular properties of the glucose tracer, many patients suffering from non-malignant diseases such as inflammatory or infectious diseases may also derive clinical benefit from the appropriate use of metabolic imaging. Large vessel vasculitides such as giant cell arteritis and Takayasu arteritis are other examples that may potentially extend the field of 18FDG PET indications. The purpose of the present article is to assess the feasibility of metabolic imaging in vasculitis on the basis of the current literature data. In particular, the clinical context and the 18FDG imaging patterns seen in patients with large vessel vasculitis are analysed in order to identify potential indications for metabolic imaging.

Whole-body 18FDG positron emission tomography in the staging of non-small cell lung cancer

Despite advances in morphological imaging, some patients with lung cancer are found to have nonresectable disease at surgery or die of recurrence within yr of surgery. We performed a prospective study in 109 patients to compare the accuracy of whole-body positron emission tomography (PET) using fluorine-18 deoxyglucose (18FDG) and conventional imaging (CI) methods for the staging of non-small cell lung cancer (NSCLC). When CI or PET study suggested metastatic disease, confirmation was obtained by biopsy or follow-up information. As compared to CI, 18FDG-PET correctly changed the N stage in 22 patients (33%) and the M stage in 15 patients (14%). For the detection of distant metastases, PET study showed five false-positive sites and no false-negative cases. Currently, the accuracy of PET in the detection of M stage is 96%. Our study shows that visual interpretation of whole-body fluorine-18 deoxyglucose-positron emission tomography images can improve the diagnostic accuracy in the staging of non-small cell lung cancer. Further experience is needed to establish if metabolic imaging would be a cost-effective tool in the future management of lung cancer.

18F-FDG PET Uptake Characterization Through Texture Analysis: Investigating the Complementary Nature of Heterogeneity and Functional Tumor Volume in a Multi–Cancer Site Patient Cohort

Intratumoral uptake heterogeneity in 18F-FDG PET has been associated with patient treatment outcomes in several cancer types. Textural feature analysis is a promising method for its quantification. An open issue associated with textural features for the quantification of intratumoral heterogeneity concerns its added contribution and dependence on the metabolically active tumor volume (MATV), which has already been shown to be a significant predictive and prognostic parameter. Our objective was to address this question using a larger cohort of patients covering different cancer types. Methods: A single database of 555 pretreatment 18F-FDG PET images (breast, cervix, esophageal, head and neck, and lung cancer tumors) was assembled. Four robust and reproducible textural feature–derived parameters were considered. The issues associated with the calculation of textural features using co-occurrence matrices (such as the quantization and spatial directionality relationships) were also investigated. The relationship between these features and MATV, as well as among the features themselves, was investigated using Spearman rank coefficients for different volume ranges. The complementary prognostic value of MATV and textural features was assessed through multivariate Cox analysis in the esophageal and non–small cell lung cancer (NSCLC) cohorts. Results: A large range of MATVs was included in the population considered (3–415 cm3; mean, 35; median, 19; SD, 50). The correlation between MATV and textural features varied greatly depending on the MATVs, with reduced correlation for increasing volumes. These findings were reproducible across the different cancer types. The quantization and calculation methods both had an impact on the correlation. Volume and heterogeneity were independent prognostic factors (P = 0.0053 and 0.0093, respectively) along with stage (P = 0.002) in non–small cell lung cancer, but in the esophageal tumors, volume and heterogeneity had less complementary value because of smaller overall volumes. Conclusion: Our results suggest that heterogeneity quantification and volume may provide valuable complementary information for volumes above 10 cm3, although the complementary information increases substantially with larger volumes.

Detecting consciousness in a total locked-in syndrome: An active event-related paradigm

Total locked-in syndrome is characterized by tetraplegia, anarthria and paralysis of eye motility. In this study, consciousness was detected in a 21-year-old woman who presented a total locked-in syndrome after a basilar artery thrombosis (49 days post-injury) using an active event-related paradigm. The patient was presented sequences of names containing the patients own name and other names. The patient was instructed to count her own name or to count another target name. Similar to 4 age- and gender-matched healthy controls, the P3 response recorded for the voluntarily counted own name was larger than while passively listening. This P3 response was observed 14 days before the first behavioral signs of consciousness. This study shows that our active event-related paradigm allowed to identify voluntary brain activity in a patient who would behaviorally be diagnosed as comatose.

(18)F-FDG PET imaging of rheumatoid knee synovitis correlates with dynamic magnetic resonance and sonographic assessments as well as with the serum level of metalloproteinase-3.

PurposeThe aim of this study was to assess rheumatoid arthritis (RA) synovitis with positron emission tomography (PET) and 18F-fluorodeoxyglucose (18F-FDG) in comparison with dynamic magnetic resonance imaging (MRI) and ultrasonography (US).MethodsSixteen knees in 16 patients with active RA were assessed with PET, MRI and US at baseline and 4 weeks after initiation of anti-TNF-α treatment. All studies were performed within 4 days. Visual and semi-quantitative (standardised uptake value, SUV) analyses of the synovial uptake of FDG were performed. The dynamic enhancement rate and the static enhancement were measured after i.v. gadolinium injection and the synovial thickness was measured in the medial, lateral patellar and suprapatellar recesses by US. Serum levels of C-reactive protein (CRP) and metalloproteinase-3 (MMP-3) were also measured.ResultsPET was positive in 69% of knees while MRI and US were positive in 69% and 75%. Positivity on one imaging technique was strongly associated with positivity on the other two. PET-positive knees exhibited significantly higher SUVs, higher MRI parameters and greater synovial thickness compared with PET-negative knees, whereas serum CRP and MMP-3 levels were not significantly different. SUVs were significantly correlated with all MRI parameters, with synovial thickness and with serum CRP and MMP-3 levels at baseline. Changes in SUVs after 4 weeks were also correlated with changes in MRI parameters and in serum CRP and MMP-3 levels, but not with changes in synovial thickness.Conclusion18F-FDG PET is a unique imaging technique for assessing the metabolic activity of synovitis. The PET findings are correlated with MRI and US assessments of the pannus in RA, as well as with the classical serum parameter of inflammation, CRP, and the synovium-derived parameter, serum MMP-3. Further studies are warranted to establish the place of metabolic imaging of synovitis in RA.

Noninvasive Assessment of Crohn's Disease Intestinal Lesions with 18F-FDG PET/CT

Pilot studies have shown good sensitivity and specificity for 18F-FDG PET in detecting gastrointestinal lesions of Crohns disease. The combination of 18F-FDG PET with CT may further improve the localization and characterization of lesions with increased 18F-FDG uptake. Our aim was to assess the use of 18F-FDG PET/CT in evaluating the activity and location of Crohns disease along the gastrointestinal tract. Methods: After giving informed consent, 22 patients with Crohns disease were prospectively studied. They underwent 18F-FDG PET/CT, followed by ileocolonoscopy within 1 wk (mean, 2 d). The Crohns disease activity index (CDAI) was calculated, and serum C-reactive protein (CRP) and fecal calprotectin were measured before endoscopy. The Crohns disease endoscopy index of severity (CDEIS) was calculated during endoscopy. The global CDEIS score and endoscopic subscores for various ileocolonic segments were used for analysis. Results: Globally, 95 intestinal and colonic segments in 22 patients were analyzed. 18F-FDG PET/CT detected 35 of 48 endoscopically affected segments (sensitivity for the detection of endoscopic lesions, 72.9%). The sensitivity of 18F-FDG PET/CT for the detection of severe endoscopic lesions (deep ulcers and strictures) was 100% (14/14). The global PET/CT score significantly correlated with CDEIS (r = 0.51; 95% confidence interval [CI], 0.09–0.77; P = 0.017), CDAI (r = 0.58; 95% CI, 0.17–0.80; P = 0.005), and CRP (r = 0.56; 95% CI, 0.19–0.81; P = 0.007). Conclusion: 18F-FDG PET/CT was globally well correlated to the clinical, endoscopic, and biologic activity of Crohns disease. Above all, this technique had a good sensitivity for the detection of intestinal and colonic segments with moderate to severe mucosal lesions. The potential impact of this promising tool on the global management of patients with Crohns disease should be further evaluated in prospective studies.