Compared vulnerabilities to small cardiac motions between different cameras used for myocardial perfusion imaging.

This phantom-based study was aimed to determine whether cardiac CZT-cameras, which provide an enhanced spatial resolution and image contrast compared to Anger cameras, are similarly affected by small cardiac motions. Translations of a left ventricular (LV) insert at half-SPECT acquisitions through six possible orthogonal directions and with 5- or 10-mm amplitude were simulated on the Discovery NM-530c and DSPECT CZT-cameras and on an Anger Symbia T2 camera equipped with an astigmatic (IQ.SPECT) or conventional parallel-hole collimator (Conv.SPECT). SPECT images were initially reconstructed as currently recommended for clinical routine. The heterogeneity in recorded activity from the 17 LV segments gradually increased between baseline and motions simulated at 5- and 10-mm amplitudes with all cameras, although being higher for Anger- than CZT-cameras at each step and resulting in a higher mean number of artifactual abnormal segments (at 10-mm amplitude, Conv.SPECT: 3.7; IQ.SPECT: 1.8, Discovery: 0.7, DSPECT: 0). However, this vulnerability to motion was markedly (1) decreased for Conv.SPECT reconstructed without the recommended Resolution Recovery algorithm and (2) increased for DSPECT reconstructed without the recommended cardiac model. CZT-cameras and especially the DSPECT appear less vulnerable to small cardiac motions than Anger-cameras although these differences are strongly dependent on reconstruction parameters.

Impact of data-driven cardiac respiratory motion correction on the extent and severity of myocardial perfusion defects with free-breathing CZT SPECT.

BACKGROUND: We previously reported the clinical feasibility and positive impact on image characteristics of a data-driven cardiac respiratory motion (RM) correction method (REGAT) applicable to CZT SPECT myocardial perfusion imaging (MPI). Here, we evaluate its impact on the extent and severity of myocardial perfusion defects (MPD). METHODS: We included 25 patients having a 1-day 99mTc-Tetrofosmin stress/rest MPI acquired with multi-pinhole CZT SPECT. Acquisitions were processed with REGAT to generate mean RM gated SPECT. These were summed either after (R-SPECT) or without realignment (NR-SPECT). We noted the maximal cardiac RM shift in the 3 axes of the left ventricle (LV). Both visual and semi-quantitative analyses of myocardial tracer uptake were realized. Studies were classified as having an impact on the extent/severity of MPD with REGAT if ≥1 segment presented a severity score changing by ≥1 level between NR-SPECT and R-SPECT. An impact on the extent of MPD was considered present if at least 1 segment shifted from normal (score = 0) to abnormal (score different from 0) or inversely. RESULTS: Cardiac RM was >10 mm in 55% of studies. With visual and semi-quantitative analyses, an impact on the extent/severity MPD was observed in 14% of all studies (7/49) and 60% of studies with cardiac RM >15 mm. An impact on the extent of MPD was observed in 5 of the 7 upper listed studies. All studies presenting an impact on MPD had RM in the anterior to inferior LV axis >10 mm. CONCLUSIONS: A substantial number of MPI studies presented significant cardiac RM. Cardiac RM compensation showed a frequent impact on the extent/severity of MPD.

A new era in gated myocardial perfusion imaging: Feasibility of data-driven cardiac contraction gating with multiple pinhole CZT SPECT.

BACKGROUND: We previously validated the use of a data-driven cardiac respiratory-motion (RM) correction method (REGAT) applicable to CZT SPECT myocardial perfusion imaging (MPI). In this study, we adapted the same process used with REGAT for RM to generate data-driven cardiac contraction triggers and corresponding cardiac contraction-gated SPECT studies (GSPECT-DD). We aimed to study its feasibility and compare its performances to GSPECT studies generated with ECG monitor-based triggers (GSPECT-ECG). METHODS: We included seven non-consecutive randomly chosen patients addressed for 1-day 99mTc-Tetrofosmin stress/rest MPI acquired with multi-pinhole CZT SPECT. We studied the degree of agreement between GSPECT-DD and GSPECT-ECG for the classification of acquired images into the 16 categories of mean cardiac cycle, and compared between the two methods the cine image quality and global LV systolic function of reconstructed studies. RESULTS: We found almost perfect agreement between cardiac contraction triggers generated with data-driven and ECG monitor-based methods. As compared to GSPECT-ECG, GSPECT-DD provided comparable and well-correlated LV global systolic function parameters and similar cine image quality at both stress and rest. CONCLUSIONS: Data-driven cardiac contraction gating using REGAT is feasible with low-dose and high-dose MPI CZT SPECT. It provides GSPECT-DD studies comparable to GSPECT-ECG.

Feasibility of data-driven cardiac respiratory motion correction of myocardial perfusion CZT SPECT: A pilot study.

BACKGROUND: We developed a data-driven respiratory motion (RM) correction method (REGAT program) for multiple-pinhole detector CZT SPECT. We verified its clinical feasibility with myocardial perfusion imaging (MPI) and studied its impact on image characteristics. METHODS: This retrospective study included 18 patients having stress/rest 99mTc-Tetrofosmin MPI SPECT. List mode was acquired on CZT SPECT and processed with REGAT. REGAT generates reconstructed RM-gated volumes that are summed either without realignment (NR-SPECT) or after realignment (R-SPECT). For both stress and rest, we calculated the maximal RM in the 3 axis, and image characteristics of both R-SPECT and NR-SPECT: minimum left ventricular (LV) cavity counts (LV-Min), maximum LV myocardial counts (LV-Max), LV contrast, and FWHM of both anterior (FWHM-ant) and inferior (FWHM-inf) LV myocardial walls. RESULTS: At both stress and rest, cranio-caudal motion was the dominant axial movement and REGAT had a positive impact on image characteristics as reflected by variations between R-SPECT and NR-SPECT in LV-Min, LV-Max, FWHM-ant, FWHM-inf, and contrast. These latter were well correlated to the amplitude of cranio-caudal motion at both stress and rest. CONCLUSIONS: Data-driven RM correction of MPI acquired with CZT SPECT is clinically feasible and easily applicable. It presents interesting impact on image characteristics.

Nanovectorization of DNA Through Cells Using Protamine Complexation.

Carbon nanotubes (CNT) are currently used as a promising family of nanovectors able to deliver different types of therapeutic molecules. Several applications dealing with CNT used as drug nanocarriers have been developed since their ability to penetrate into the cells has been proved. CNT can thus load several active molecules to various cells. In this paper, we will use molecular dynamic simulation to describe theoretically the potential of CNT to transport and deliver DNA through the formation of protamine-DNA-CNT complex.

Utility of 18F-fluoro-dexoxyglucose positron emission tomography for the diagnosis of polymyalgia rheumatica: a controlled study.

OBJECTIVES: To compare (18)F-fluoro-dexoxyglucose PET/CT (FDG-PET/CT) findings in patients with polymyalgia rheumatica (PMR) and controls without rheumatologic disease. METHODS: We retrospectively included 50 patients with a diagnosis of PMR as well as 53 patients with a neoplasm as a control group. All patients underwent FDG-PET/CT. Seventeen hotspots were analysed. We performed a semi-quantitative analysis of FDG uptake (4-point score from 0 to 3). The cut-offs for the number of sites with high activity and for FDG uptake score were assessed using receiver operating characteristics curves and odds ratios (ORs). RESULTS: The two groups were comparable for the median patient age (69.3 years for PMR vs 68.1 for controls). Significant differences between the two groups were found for FDG uptake score (1.12 vs 0.34, P < 0.00001) and for the number of sites with significant uptake (score ⩾ 2): 6.36 sites vs 1.49 sites (P < 0.00001). The presence of three or more sites with significant uptake was correlated with the diagnosis of PMR with 74% sensitivity and 79% specificity (OR = 10.8). For the FDG uptake score, the cut-off was 0.53 (sensitivity 80%, specificity 77%, OR = 13.6). We found significant differences in all sites for FDG uptake score and the number of sites with significant uptake, particularly marked for shoulders, ischial tuberosities and interspinous bursitis (P < 0.00001 for FDG uptake score). CONCLUSION: Our results suggest that the number of sites with significant FDG uptake and the uptake score could be relevant criteria for the diagnosis of PMR.

Theoretical demonstration of the potentiality of boron nitride nanotubes to encapsulate anticancer molecule.

Anticancer drug transport is now becoming an important scientific challenge since it would allow localizing the drug release near the tumor cell, avoiding secondary medical effects. We present theoretical results, based on density functional theory and molecular dynamics simulations, which demonstrate the stability of functionalized single (10,10) boron nitride nanotubes (BNNTs) filled with anticancer molecule such as carboplatin (CPT). For this functionalized system we determine the dependence of the adsorption energy on the molecule displacement near the inner BNNTs surface, together with their local morphological and electrical changes and compare the values to the adsorption energy obtained on the outer surface. Quantum simulations show that the most stable physisorption state is located inside the nanotube, with no net charge transfer. This demonstrates that chemotherapeutic encapsulation is the most favorable way to transport drug molecules. The solvent effect and dispersion repulsion contributions are then taken into account using molecular dynamics simulations. Our results confirm that carboplatin therapeutic agents are not affected when they are adsorbed inside BNNTs by the surrounding water molecules.

Sentinel lymph node biopsy in melanoma: our 8-year clinical experience in a single French institute (2002-2009).

BACKGROUND: Since the introduction of sentinel lymph node biopsy (SLNB), its use as a standard of care for patients with clinically node-negative cutaneous melanoma remains controversial. We wished to evaluate our experience of SLNB for melanoma. METHODS: A single center observational cohort of 203 melanoma patients with a primary cutaneous melanoma (tumour thickness > 1 mm) and without clinical evidence of metastasis was investigated from 2002 to 2009. Head and neck melanoma were excluded. SLN was identified following preoperative lymphoscintigraphy and intraoperative gamma probe interrogation. RESULTS: The SLN identification rate was 97%. The SLN was tumor positive in 44 patients (22%). Positive SLN was significantly associated with primary tumor thickness and microscopic ulceration. The median follow-up was 39.5 (5-97) months. Disease progression was significantly more frequent in SLN positive patients (32% vs 13%, p = 0.002). Five-year DFS and OS of the entire cohort were 79.6% and 84.6%, respectively, with a statistical significant difference between SLN positive (58.7% and 69.7%) and SLN negative (85% and 90.3%) patients (p = 0.0006 and p = 0.0096 respectively). Postoperative complications after SLNB were observed in 12% of patients. CONCLUSION: Our data confirm previous studies and support the clinical usefulness of SLNB as a reliable and accurate staging method in patients with cutaneous melanoma. However, the benefit of additional CLND in patients with positive SLN remains to be demonstrated.

Could 18-FDG PET-CT Radiomic Features Predict the Locoregional Progression-Free Survival in Inoperable or Unresectable Oesophageal Cancer?

Background: We evaluated the value of pre-treatment positron-emission tomography−computed tomography (PET-CT)-based radiomic features in predicting the locoregional progression-free survival (LR-PFS) of patients with inoperable or unresectable oesophageal cancer. Material and Methods: Forty-six patients were included and 230 radiomic parameters were extracted. After a principal component analysis (PCA), we identified the more robust radiomic parameters, and we used them to develop a heatmap. Finally, we correlated these radiomic features with LR-PFS. Results: The median follow-up time was 17 months. The two-year LR-PFS and PFS rates were 35.9% (95% CI: 18.9−53.3) and 21.6% (95%CI: 10.0−36.2), respectively. After the correlation analysis, we identified 55 radiomic parameters that were included in the heatmap. According to the results of the hierarchical clustering, we identified two groups of patients presenting statistically different median LR-PFSs (22.8 months vs. 9.9 months; HR = 2.64; 95% CI 0.97−7.15; p = 0.0573). We also identified two radiomic features ("F_rlm_rl_entr_per" and "F_rlm_2_5D_rl_entr") significantly associated with LR-PFS. Patients expressing a "F_rlm_2_5D_rl_entr" of <3.3 had a better median LR- PFS (29.4 months vs. 8.2 months; p = 0.0343). Patients presenting a "F_rlm_rl_entr_per" of <4.7 had a better median LR-PFS (50.4 months vs. 9.9 months; p = 0.0132). Conclusion: We identified two radiomic signatures associated with a lower risk of locoregional relapse after CRT.

Unusual uptakes on 18F-fluorocholine positron emission tomography/computed tomography (PET/CT): a retrospective study of 368 prostate cancer patients referred for a biochemical recurrence or an initial staging.

BACKGROUND: 18F-fluorocholine positron emission tomography/computed tomography (F-choline PET/CT) is considered a cornerstone in the staging and restaging of patients with prostate cancer (PCa). The aim of this study was to retrospectively assess unusual uptakes in patients who underwent a F-choline PET/CT for the initial staging or for the restaging of a relapsing PCa. METHODS: Three hundred and sixty-eight PCa patients were staged or restaged using F-choline PET/CT. Unusual uptakes were defined as uptakes occurring outside the usual paths of diffusion of PCa or as uptake in bone with a clear morphological evidence of nonmetastatic lesion. RESULTS: We found unusual uptakes in 47/368 patients (12.8%). Among them, 41/47 presented with benign F-choline uptake, usually within lymph nodes, due to inflammatory processes (22/47). Other benign processes were found in: thyroid (3/47), adrenal gland (3/47), brain (2/47), liver (1/47), bowel (3/47), frontal sinus (1/47), lungs (4/47), parotid gland (1/47) and bone (1/47). The six remaining patients presented with a second cancer, including lymphoma (1/47), non-small cell lung cancer (4/47) and neuroendocrine tumor (1/47). CONCLUSIONS: unusual uptakes on F-choline PET/CT are quite frequent and should be explored since they may correspond to non-PCa.

Muscle involvement on 18F-FDG PET-CT in polymyalgia rheumatica. A controlled retrospective study of 101 patients.

18F-fluoro deoxy glucose PET scanner (18F-FDG-PET-CT) has shown its interest in the diagnosis of polymyalgia rheumatica (PMR) and makes possible to evaluate the metabolic activity of the entire musculoskeletal system and in particular muscular structures. The purpose of this study was to evaluate muscle involvement using 18F-FDG-PET-CT in the case of PMR, compared to a non PMR population. METHODS: This is a monocentric retrospective study of patients with PMR (ACR/EULAR 2012 criteria) who had an 18F-FDG-PET-CT examination. A control group composed of subjects without rheumatological manifestations who had such an examination as part of neoplastic research or follow-up of neoplastic diseases was also evaluated. The PET assessment included 17 sites suggesting a PMR, as previously reported. Areas of muscle hypermetabolism were classified in the same way according to the same semi quantitative classification. Muscle activity sites were identified. A comparison of patients with PMR with and without muscle damage was performed using the exact Mann-Whitney or Fisher test. RESULTS: Two hundred and one cases were examined, involving 101 PMRs (mean age 68.6 years) and 100 controls (mean age 67.7 years). Overall, PET muscle damage was observed in 34 cases (34%) in PMR and 10 cases (10%) in controls (P=0.004). Lesions are bi or multi-focal in half of the cases. The affected muscle sites are: spinal muscles 19, scapular girdle 14, pelvic girdle 13, and thigh 6. Fasciitis was found in 3 cases. In patients with PMR, PET muscle involvement was not associated with age, CRP or overall PMR PET score. CONCLUSION: Muscle damage assessed by 18F-Fluorodeoxyglucose PET-CT is common in PMR (1/3 of cases), located at the usual sites of disease symptoms, without association with age, CRP levels or the overall PET PMR score. The muscle must be carefully evaluated during a PET examination in cases of PMR.

Improved photodynamic effect through encapsulation of two photosensitizers in lipid nanocapsules.

Photodynamic therapy (PDT) has developed into a new clinical and non-invasive treatment for cancer over the past 30 years. By the combination of three non-toxic partners, i.e. a photosensitizer (PS), molecular oxygen (O2) and light, cytotoxic reactive oxygen species (ROS) are locally produced leading to irreversible vascular and cellular damage. In the present study, we report for the first time that the combination of two photosensitizers (2 PSs: Protoporphyrin IX, PpIX and Hypericin, Hy) loaded in the same lipid nanocapsules (LNCs) leads to enhanced photodynamic therapy efficiency when compared with previously reported systems. The 2 PS-loaded LNCs are shown to increase the in vitro phototoxicity at the nanomolar range (IC50 = 274 and 278 nM on HeLa and MDA-MB-231 cell lines, respectively), whereas the corresponding single PS-loaded LNCs at the same concentration exhibit a phototoxicity two times lower. Intracellular localization in HeLa cells indicates a subcellular asymmetry of PpIX and Hy, in the plasma, ER membranes and round internal structures. The biodistribution of LNCs was studied upon different routes of injection into Swiss nude mice; based on the obtained data, LNCs were injected intratumorally and used to slow the growth of xenograft tumors in mice. The results obtained in this study suggest that the combination of two or more PSs may be a promising strategy to improve the efficacy of conventional photodynamic therapy as well as to reduce dark toxicity.

Bilateral Huge Incidentalomas of Isolated Adrenal Metastases From Unknown Primary Melanoma Revealed by 18F-FDG PET/CT.

FDG PET/CT has high sensitivity and specificity for the detection of distant metastases from cutaneous melanoma. Imaging is recommended for patients with clinical suspicion of metastasis and should be considered for those with confirmed sentinel lymph node metastasis. Metastatic melanoma bears a poor prognosis. Only a complete resection improves survival, which explains the need to detect potentially unresectable disease, and most metastatic patients are ineligible for a curative surgical procedure. Here, FDG PET/CT demonstrated isolated bilateral adrenal metastases from melanoma of unknown primary. The patient underwent curative surgery, with no sign of recurrence at 48 months after surgery.

Brain Perfusion Before and After Surgical Treatment of Moyamoya Disease.

Moyamoya disease is characterized by bilateral progressive terminal internal carotid arteries steno-occlusion. In this patient, the disease affected middle cerebral arteries and was disclosed after a left frontal cerebral infarction. Brain HMPAO perfusion scintigraphy with acetazolamide challenge, obtained before surgical treatment, demonstrates an extended bilateral frontal hypoperfusion with a vascular steal phenomenon. The same examination obtained after surgical treatment demonstrates a frank improvement in basal brain vascularization, with nearly complete correction of vascular steal phenomenon. HMPAO brain scintigraphy is a very useful tool in the assessment of moyamoya disease severity before surgery and for the evaluation of treatment efficiency.

FDG Brain PET/CT Revealing Bilateral Thalamostriatal Activation During a Symptomatic Episode in a Patient With Kleine-Levin Syndrome.

We report the case of a 14-year-old girl with clinically diagnosed Kleine-Levin syndrome. Electroencephalogram and brain MRI were unremarkable. An FDG PET/CT scan was acquired during a symptomatic episode, while she was asleep, and another PET scan was obtained when she was asymptomatic, awake, and quiet. Comparison of both examinations demonstrated a bilateral activation of thalami, caudate nuclei, and lenticular nuclei. These findings may be linked to the implication of thalamostriatal structures in the regulation of sleep and wakefulness.

Carbon nanotubes as gene carriers: Focus on internalization pathways related to functionalization and properties.

Carbon nanotubes represent promising transporters for delivery of DNA and other biomolecules into living cells. Various methods of CNTs surface functionalization have been developed. These are essential to improve CNTs dispersibility and permit their interactions with biological structures that broaden their use in advanced biomedical applications. The present review discusses the different single walled carbon nanotubes and multiwalled carbon nanotubes functionalization methods, leading to the formation of optimized and functionalized-CNT complexes with DNA. F-CNTs are recognized as efficient and promising gene carriers. Emphasis is then placed on the processes used by f-CNTs/DNA complexes to cross cell membranes. Energy independent pathways and uptake mechanisms dependent on energy, such as endocytosis or phagocytosis, are reported by many studies, and if these mechanisms seem contradictory at first sight, a detailed review of the literature illustrates that they are rather complementary. Preferential use of one or the other depends on the DNA and CNTs chemical nature and physical parameters, experimental procedures and cell types. STATEMENT OF SIGNIFICANCE: Efficient non-viral gene delivery is desirable, yet challenging. CNTs appear as a promising solution to penetrate into cells and successfully deliver DNA. Moreover, the field of use of CNTs as gene carrier is large and is currently growing. This critical review summarizes the development and evaluation of CNTs as intracellular gene delivery system and provides an overview of functionalized CNTs/DNA cellular uptake mechanisms, depending on several parameters of CNTs/DNA complexes.