Functional PET Neuroimaging in Consciousness Evaluation: Study Protocol

Ensuring a robust and reliable evaluation of coma deepness and prognostication of neurological outcome is challenging. We propose to develop PET neuroimaging as a new diagnostic and prognosis tool for comatose patients using a recently published methodology to perform functional PET (fPET). This exam permits the quantification of task-specific changes in neuronal metabolism in a single session. The aim of this protocol is to determine whether task-specific changes in glucose metabolism during the acute phase of coma are able to predict recovery at 18 months. Participation will be proposed for all patients coming for a standard PET-CT in our center in order to evaluate global cerebral metabolism during the comatose state. Legally appointed representative consent will be obtained to slightly modify the exam protocol: (1) 18F-fluorodeoxyglucose (18F-FDG) bolus plus continuous infusion instead of a simple bolus and (2) more time under camera to perform dynamic acquisition. Participants will undergo a 55-min fPET session with a 20% bolus + 80% infusion protocol. Two occurrences of three block (5-min rest, 10-min auditory stimulation and 10-min emotional auditory stimulation) will be performed after reaching equilibrium of FDG arterial concentration. We will compare the regional brain metabolism at rest and during the sessions of auditory and emotional auditory stimulation to search for a determinant of coma recovery (18 months of follow-up after the exam). Emotional auditory stimulation should induce an activation of: the auditory cortex, the consciousness areas and the neural circuitry for emotion (function to coma deepness). An activation analysis will be carried out to highlight regional brain activation using dedicated custom-made software based on Python statistical and image processing toolboxes. The association between activation levels and the Coma Recovery Scale-Revisited (CRS-R) will be assessed using multivariate analysis. If successful, the results from this study will help improve coma prognosis evaluation based on the pattern of neuronal metabolism at the onset of the pathology. The study protocol, rationale and methods are described in this paper

Analysis of differences between 99mTc-MAA SPECT- and 90Y-microsphere PET-based dosimetry for hepatocellular carcinoma selective internal radiation therapy

International audienceBackground: The aim of this study was to compare predictive and post-treatment dosimetry and analyze the differences, investigating factors related to activity preparation and delivery, imaging modality used, and interventional radiology.Methods: Twenty-three HCC patients treated by selective internal radiation therapy with 90Y glass microspheres were included in this study. Predictive and post-treatment dosimetry were calculated at the voxel level based on 99mTc-MAA SPECT/CT and 90Y-microsphere PET/CT respectively. Dose distribution was analyzed through mean dose, metrics extracted from dose-volume histograms, and Dice similarity coefficients applied on isodoses. Reproducibility of the radiological gesture and its influence on dose deviation was evaluated.Results: 90Y delivered activity was lower than expected in 67% (16/24) of the cases mainly due to the residual activity. A mean deviation of − 6 ± 11% was observed between the delivered activity and the 90Y PET’s FOV activity. In addition, a substantial difference of − 20 ± 8% was measured on 90Y PET images between the activity in the liver and in the whole FOV. After normalization, 99mTc-MAA SPECT dosimetry was highly correlated and concordant with 90Y-microsphere PET dosimetry for all dose metrics evaluated (ρ = 0.87, ρc = 0.86, P = 3.10−8 and ρ = 0.91, ρc = 0.90, P = 7.10−10 for tumor and normal liver mean dose respectively for example). Besides, mean tumor dose deviation was lower when the catheter position was identical than when it differed (16 Gy vs. 37 Gy, P = 0.007). Concordance between predictive and post-treatment dosimetry, evaluated with Dice similarity coefficients applied on isodoses, significantly correlated with the distance of the catheter position from artery bifurcation (P = 0.04, 0.0004, and 0.05, for 50 Gy, 100 Gy, and 150 Gy isodoses respectively).Conclusions: Discrepancies between planned activity and activity measured on 90Y PET images were observed and seemed to be mainly related to clinical hazards and equipment issues. Predictive vs. post-treatment comparison of relative dose distributions between tumor and normal liver showed a good correlation and no significant difference highlighting the predictive value of 99mTc MAA SPECT/CT-based dosimetry. Besides, the reproducibility of catheter tip position appears critical in the agreement between predictive and actual dose distribution

Hepatobiliary Scintigraphy and Glass 90Y Radioembolization with Personalized Dosimetry: Dynamic Changes in Treated and Nontreated Liver

International audienceBackground: The functional changes that occur over time in the liver following 90Y-radioembolization (RE) using personalized dosimetry (PD) remain to be investigated.Methods: November 2016–October 2019: we retrospectively included hepatocellular carcinoma (HCC) patients treated by 90Y-glass RE using PD, who underwent hepatobiliary scintigraphy (HBS) at baseline and at 15 days, 1, 2, 3, and 6 months after RE.Results: There were 16 patients with unilobar disease (100%) included, and 64 HBS were performed. Whole liver function significantly decreased over time. The loss was maximal at 2 weeks: −32% (p = 0.002) and remained below baseline at 1 (−15%; p = 0.002), 2 (−25%; p < 0.001), and 3 months (−16%; p = 0.027). No radioembolization-induced liver disease was observed. Treated liver function strongly decreased to reach −64% (p < 0.001) at 2 months. Nontreated liver function decreased at 2 weeks (−21%; p = 0.027) and remained below baseline before reaching +20% (p = 0.002) and +59% (p < 0.001) at 3 and 6 months, respectively. Volumetric and functional changes exhibited parallel evolutions in the treated livers (p = 0.01) but independent evolutions in the nontreated livers (p = 0.08).Conclusion: RE using PD induces significant regional changes in liver function over time. As early as 15 days following RE, both the treated and nontreated livers showed a decreased function. Nontreated liver function recovered after 3 months and greatly increased afterwards

Retrospective Voxel-Based Dosimetry for Assessing the Ability of the Body-Surface-Area Model to Predict Delivered Dose and Radioembolization Outcome

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Personalised versus standard dosimetry approach of selective internal radiation therapy in patients with locally advanced hepatocellular carcinoma (DOSISPHERE-01): a randomised, multicentre, open-label phase 2 trial

International audienceBACKGROUND: All randomised phase 3 studies of selective internal radiation therapy for advanced hepatocellular carcinoma published to date have reported negative results. However, these studies did not use personalised dosimetry. We aimed to compare the efficacy of a personalised versus standard dosimetry approach of selective internal radiation therapy with yttrium-90-loaded glass microspheres in patients with hepatocellular carcinoma.METHODS: DOSISPHERE-01 was a randomised, multicentre, open-label phase 2 trial done at four health-care centres in France. Patients were eligible if they were aged 18 years or older and had unresectable locally advanced hepatocellular carcinoma, at least one measurable lesion 7 cm or more in size, a hepatic reserve of at least 30% after selective internal radiation therapy, no extrahepatic spread (other than to the lymph nodes of the hilum, with a lesion &lt;2 cm in size), and no contraindications to selective internal radiation therapy, as assessed by use of a technetium-99m macro-aggregated albumin scan. Patients were randomly assigned (1:1) by use of a permutated block method, with block sizes of four and without stratification, to receive either standard dosimetry (120 ± 20 Gy) targeted to the perfused lobe; standard dosimetry group) or personalised dosimetry (≥205 Gy targeted to the index lesion; personalised dosimetry group). Investigators, patients, and study staff were not masked to treatment. The primary endpoint was the investigator-assessed objective response rate in the index lesion, according to European Association for the Study of the Liver criteria, at 3 months after selective internal radiation therapy in the modified intention-to-treat population. Safety was assessed in all patients who received at least one selective internal radiation therapy injection, and analysed on the basis of the treatment actually received (defined by central dosimetry assessment). The trial is registered with ClinicalTrials.gov, NCT02582034, and has been completed.FINDINGS: Between Dec 5, 2015, and Jan 4, 2018, 93 patients were assessed for eligibility. Of these patients, 60 were randomly assigned: 31 to the personalised dosimetry group and 29 to the standard dosimetry group (intention-to-treat population). 56 (93%) patients (28 in each group) were treated (modified intention-to-treat population). In the modified intention-to-treat population, 20 (71% [95% CI 51-87]) of 28 patients in the personalised dosimetry group and ten (36% [19-56]) of 28 patients in the standard dosimetry group had an objective response (p=0·0074). In the safety analysis population, a least one serious adverse event was reported in seven (20%) of the 35 patients who received personalised dosimetry, and in seven (33%) of the 21 patients who received standard dosimetry. The most frequent (ie, occurring in &gt;5% of patients) grade 3 or higher adverse events were ascites (one [3%] patient who received personalised dosimetry vs two [10%] patients who received standard dosimetry), hepatic failure (two [6%] vs none), lymphopenia (12 [34%] vs nine [43%]), increased aspartate aminotransferase concentrations (three [9%] vs two [10%]), increased alanine aminotransferase concentrations (three [9%] vs none), anaemia (two [6%] vs one [5%]), gastrointestinal haemorrhage (none vs two [10%]), and icterus (none vs two [10%]). One treatment-related death occurred in each group.INTERPRETATION: Compared with standard dosimetry, personalised dosimetry significantly improved the objective response rate in patients with locally advanced hepatocellular carcinoma. The results of this study suggest that personalised dosimetry is likely to improve outcomes in clinical practice and should be used in future trials of selective internal radiation therapy. FUNDING: Biocompatibles UK, a Boston Scientific Group company

Mean activity concentration estimated from 15 cm diameter circular Regions of Interest (ROIs) on 15 consecutive slices and accuracy.

<p>Data acquired on the 4 PET systems used in 2D mode. Activity concentration in images and in phantom expressed in kBq/mL. Standard deviation (SD), accuracy and maximum deviation are in %.</p

Central profile on a transverse slice of phantoms.

<p>Data are normalized to the maximum value intensity of the profile. No abnormality was seen.</p

Observed artefacts on images acquired on uniform phantom.

<p>Display scale is [0; 100%]. A: no artefacts (site 9), B: LOR-RAMLA concentric ring artefacts (site 6), C: FBP concentric ring artefacts (site 4).</p

Dose calibrator reproducibility and accuracy results.

<p>Repeated measurements of certified standard source (⁶⁸Ge) on the dose calibrators of 11 sites. Standard source activity was calculated by applying decay calculation between the calibration date and the measurements date. Measurements expressed in MBq. Standard deviation (SD) and accuracy are in %.</p

Mean activity concentration estimated from 15 cm diameter circular Regions of Interest (ROIs) on 15 consecutive slices and accuracy.

<p>Data acquired on the 8 PET systems used in 3D mode. Activity concentration in images and in phantom expressed in kBq/mL. Standard deviation (SD), accuracy and maximum deviation are in %.</p