Electrical stimulation of chicken embryo development supports the Inside story scenario of human development and evolution.

Animal evolution is driven by random mutations at the genome level. However, it has long been suggested that there exist physical constraints which limit the set of possible outcomes. In craniate evolution, it has been observed that head features, notably in the genus homo, can be ordered in a morphological diagram such that, as the brain expands, the head rocks more forward, face features become less prognathous and the mouth tends to recede. One school of paleontologists suggests that this trend is wired somewhere structurally inside the anatomy, and that random modifications of genes push up or down animal forms along a pre-determined path. No actual experiment has been able to settle the dispute. I present here an experiment of electric stimulation of the head in the chicken embryo which is able to enhance the magnitude of tension forces during development. This experimental intervention causes a correlated brain shrinkage and rotatory movement of the head, congruent with tissue texture, which proves that head dilation and flexure are intimately linked. Numerical modelling explains why the brain curls when it dilates. This gives support to the idea that there exists, in the texture of the vertebrate embryo, a latent dynamic pattern for the observed paleontological trends in craniates towards homo, a concept known as Inside story.

Genetic determinism and hemispheric influence in hair whorl formation.

BACKGROUND: The mechanisms determining the laterality and the rotation direction of hair whorls are unknown. Here we report observations on twins investigating the genetic bases of whorl pattern formation. Knowing that vortex phenomena may depend on geographic effects, we also provide comparative data on whorls from children born in the Northern hemisphere (France) versus children born in the Southern hemisphere (Chile). MATERIAL AND METHODS: We retrospectively included children from three populations: (1) Northern hemisphere general population, (2) Southern hemisphere general population, and (3) same-sex Northern hemisphere twins. We recorded whorl rotation direction (clockwise, counterclockwise), whorl position (left, right, central) and twinning type. Univariate logistic models were used to screen for associations between rotation direction and whorl position. For twins, the variable of interest was binary, i.e. same rotation direction (reference class) or opposite directions for each twin pair. For controls, all single combinations were included as virtual twins, and compared to real twins. Odds ratios (OR) were compared for both hemispheres, for real twins and virtual (control) twins. RESULTS: Seventy-four (37 pairs) twins and 50 children from the general population of each hemisphere were included. The OR for opposite rotation directions between two twins was ≠1 (p = 0.017), meaning that whorls rotated preferentially in the same direction in twins. ORs were <1 for Northern and Southern hemispheres, meaning that whorls rotated preferentially in the same direction in simulated twins. OR for the Northern hemisphere (0.04 [0.03; 0.05]) was less than the OR for the Southern hemisphere (0.28 [0.24; 0.32]) with no confidence interval superimposition, indicating than counterclockwise whorls were more frequent in the Southern hemisphere (p < 0.001). CONCLUSIONS: We suggest that hair whorl formation is a genetically determined developmental process that can be influenced by extrinsic environmental factors. Our results furthermore underline the general importance of studies focused on limit phenomena that can provide insights on general developmental mechanisms. We plead for large-scale epidemiological assessments of hair whorls in several Northern and Southern hemisphere populations to confirm these surprising findings suggesting significant modulations of craniofacial development by geographic effects.

Prospective Multicentric Assessment of 68Ga-DOTANOC PET/CT in Grade 1-2 GEP-NET.

The aim of this multicentric study was to prospectively compare 68Ga-DOTANOC PET/CT versus somatostatin receptor scintigraphy (SRS) with SPECT/CT, combined with multiphasic CT scan and MRI in patients with grade 1 or 2 gastroenteropancreatic neuroendocrine tumors (GEP-NET). Patients with histologically proven grade 1 or 2 GEP-NET with suspicion of recurrence or progression, or with typical aspects of GEP-NET on morphological imaging, were explored with conventional imaging (CI): SRS with SPECT/CT, multiphasic CT scan and/or liver MRI followed by 68Ga-DOTANOC PET/CT. The gold standard was based on histology and imaging follow-up. The data of 105 patients (45 woman and 60 men; median age) were analyzed. 68Ga-DOTANOC PET/CT sensitivity was significantly higher than CI sensitivity in per-patient (98.9% vs. 88.6%, p = 0.016) and per-region (97.6% vs. 75.6%, p < 0.001) analyses, in the detection of the primary (97.9% vs. 78.7%; p = 0.016), peritoneal carcinomatosis (95% vs. 30%, p < 0.001), and bone metastases (100% vs. 33.3%, p = 0.041). 68Ga-DOTANOC PET/CT had an impact on the therapeutic management of 41.9% (44/105) patients compared to decisions based on CI explorations. Our data confirm the superiority of 68Ga-DOTANOC PET/CT over CI in the detection of peritoneal carcinomatosis and bone metastasis, as well as its strong therapeutic impact on the management of patients with grade 1-2 GEP-NETs.

Dynamics of early stages of nose morphogenesis.

The formation of sensory organs is an important developmental and evolutionary question. In the context of regenerative medicine also, it is important to know as accurately as possible how sensory organs form. The formation of ears, eyes or nose stems presumably from tissue thickenings called placodes Graham and Shimeld (J Anat 222(1):32-40, 2013), Horie et al. (Nature 560:228-232, 2018) which become these organs after processes termed inductions. However, the origin of the placodes, the mechanism of induction and the overall face organization are not understood. Recently, it has been suggested that there is a physical principle to face organization. Indeed, it has been shown that there exists a pattern of rings and rays in the early blastula which defines the position of face landmarks, especially the ears and eyes Fleury et al. (Second order division in sectors as a prepattern for sensory organs in vertebrate development, 2021), Fleury and Abourachid (Eu Phys J E 45:31, 2022). Tensions in the sectors defined by the intersections of the said rings and rays create the actual face features. I report here that a similar situation exists for the nose. This explains the robustness of face formation in the chordates phylum. By studying nasal pit formation in the chicken embryo by time-lapse (T-L) video microscopy, I show that the nasal placode originates in a narrow sector deformed by tension forces following the biaxial pattern of rings and rays mentioned above. Cells align in the pattern and exert organized forces. Further contractions of the pattern contribute to inducing the nasal pit. The observation of the early pre-pattern of lines which locks the facial features explains readily a number of facts regarding sensory organs. Especially the existence of a lacrimal canal between the eye and the nose Lefevre and Freitag (Semin Ophthalmo l 27(5-6):175-86, 2012), or of a slit connecting the nose to the mouth, the correlation between nose, mouth and eye morphogenesis Dubourg et al. (J Rare Dis 2(8), 2007), the presence of shallow valleys on the nasal and optic vesicles, the medio-lateral asymmetry of nostrils with often a bent slit Liu et al. (PLoS ONE 12: e0181928, 2017), the uneven number of nostrils in many fish Cox (J R Soc Interf 5(23):575-593, 2008) and possibly the transition between agnatha and gnathostomes Gai and Zhu (Chinese Sci Bull 57(31), 2012): all appear under this light, geometrically straightforward. The nasal pit forms in a sector of tissue which was present on the blastodic (early embryonic stage), and which is projected onto the nasal vesicle during neurulation. The nasal pit forms along a hairpin of tissue. The top part of the hairpin forms the nares, and the bottom part a groove often visible in many animals.

Deformable image registration with deep network priors: a study on longitudinal PET images.

Objective.This paper proposes a novel approach for the longitudinal registration of PET imaging acquired for the monitoring of patients with metastatic breast cancer. Unlike with other image analysis tasks, the use of deep learning (DL) has not significantly improved the performance of image registration. With this work, we propose a new registration approach to bridge the performance gap between conventional and DL-based methods: medical image registration method regularized by architecture (MIRRBA).Approach.MIRRBAis a subject-specific deformable registration method which relies on a deep pyramidal architecture to parametrize the deformation field. Diverging from the usual deep-learning paradigms,MIRRBAdoes not require a learning database, but only a pair of images to be registered that is used to optimize the network's parameters. We appliedMIRRBAon a private dataset of 110 whole-body PET images of patients with metastatic breast cancer. We used different architecture configurations to produce the deformation field and studied the results obtained. We also compared our method to several standard registration approaches: two conventional iterative registration methods (ANTs and Elastix) and two supervised DL-based models (LapIRN and Voxelmorph). Registration accuracy was evaluated using the Dice score, the target registration error, the average Hausdorff distance and the detection rate, while the realism of the registration obtained was evaluated using Jacobian's determinant. The ability of the different methods to shrink disappearing lesions was also computed with the disappearing rate.Main results.MIRRBA significantly improved all metrics when compared to DL-based approaches. The organ and lesion Dice scores of Voxelmorph improved by 6% and 52% respectively, while the ones of LapIRN increased by 5% and 65%. Regarding conventional approaches, MIRRBA presented comparable results showing the feasibility of our method.Significance.In this paper, we also demonstrate the regularizing power of deep architectures and present new elements to understand the role of the architecture in DL methods used for registration.

Vaccine-Related Lymph Nodes: The Emerging Pitfalls of 18F-Fluorocholine and 68Ga-PSMA-11 PET/CT in the Era of COVID-19 Vaccination.

PURPOSE: Vaccination against coronavirus disease 2019 (COVID-19) is currently under worldwide deployment. The consequences of this vaccination can be seen in radiology and nuclear medicine explorations with visualization of axillary lymph nodes (LNs), as observed on ultrasonography, MRI, or 18F-FDG PET/CT.We aimed to evaluate on PET/CT the incidence of vaccine-related LNs and their characteristics after COVID-19 vaccination, using several radiopharmaceuticals different from 18F-FDG. PATIENTS AND METHODS: Between February and July 2021, all consecutive patients undergoing a whole-body PET/CT for any indication using a different radiopharmaceutical from 18F-FDG were eligible for inclusion if they had received at least 1 dose of the COVID-19 vaccine. The radiopharmaceutical administered and vaccine type were recorded for each patient. The incidence of positive vaccine-related axillary and supraclavicular LNs on PET/CT was our primary finding, along with the nodes characteristics. Statistical analyses were performed for patients with prostate cancer (PCa) to determine certain interaction factors that were associated with the detection of vaccine-related LNs. RESULTS: Of the 226 patients in our cohort study, 120 patients underwent an 18F-fluorocholine PET/CT, 79 a 68Ga-PSMA-11 PET/CT, 6 an 18F-FDOPA PET/CT, and 21 a 68Ga-DOTATOC PET/CT. A total of 67.3% of patients (152/226) received BNT162b2mRNA (Pfizer-BioNTech), 26.5% (60/226) ChAdOx1-S (AstraZeneca), 4.9% (11/226) mRNA-1273 (Moderna), and 1.3% (3/226) Ad26.COV2.S (Janssen). The incidence of positive vaccine-related axillary and supraclavicular LNs was 42.5% (51/120 patients) on PET/CT using 18F-fluorocholine and 12.7% (10/79 patients) with 68Ga-PSMA-11. None of our patients undergoing 18F-FDOPA or 68Ga-DOTATOC PET/CT presented any vaccine-related lymphadenopathy. Vaccine-related LNs were statistically associated with the nature of the radiopharmaceutical (P < 10-4), with the number of vaccine doses received (P = 0.041), with a short delay between vaccination and PET/CT realization (P < 10-5), and with a higher prostate-specific antigen level for patients with PCa (P = 0.032), but not with age or vaccine type. The vaccine-related nodes appeared in 85% of the cases, in the 30 days after vaccine injection, were limited in size and uptake, and were most often limited to the axilla level 1 area. CONCLUSIONS: Detecting positive LNs after COVID-19 vaccination is not an exclusive 18F-FDG PET/CT pattern but is common on 18F-fluorocholine and possible on 68Ga-PSMA-11 PET/CT. Confronting PET/CT findings with clinical data (such as date and site of injection) seems essential in the current pandemic context, just as it does for the radiopharmaceuticals used in PCa to avoid PET/CT misinterpretation and incorrect patient treatment. For 18F-FDOPA or 68Ga-DOTATOC PET/CT, this seems to have a lesser impact.

A biaxial tensional model for early vertebrate morphogenesis.

We propose a simple biaxial tensional model which is able to reproduce at a qualitative level several aspects of early stages of vertebrate morphogenesis. The model is based on subsequent excitable contractions of an orthoradial and periclinal (radial) set of contracting lines, which generate first the basic embryonic pattern (a motile tube), and second the lateral orifices such as ears, eyes, mouth, gills, etc. An important aspect of the model is the self-arresting character of the process, akin to wound healing. At later stages, the biaxial lines may also work in extension, and this generates a developmental feedback which is quadratic with respect to curvature.

Is Glucagon Administration Compatible With FDG PET/MRI?

ABSTRACT: Digestive peristalsis generates many artifacts that limit the abdominal and pelvic MRI interpretation. Apart from the hypoglycemia treatment in patients with diabetes, glucagon analog is also indicated for the digestive peristalsis reduction to reduce MRI artifacts. However, its use in PET/MRI is not described, given the risk of interaction with the metabolism of FDG. To assess the importance of this interaction on the FDG PET images, we report FDG PET/MRI images obtained with and without glucagon analog injection.

Second-order division in sectors as a prepattern for sensory organs in vertebrate development.

We present in vivo observations of chicken embryo development which show that the early chicken embryo presents a principal structure made out of concentric rings and a secondary structure composed of radial sectors. During development, physical forces deform the main rings into axially directed, antero-posterior tubes, while the sectors roll up to form cylinders that are perpendicular to the antero-posterior axis. As a consequence, the basic structure of the chicken embryo is a series of encased antero-posterior tubes (gut, neural tube, body envelope, amnion, chorion) decorated with smaller orifices (ear duct, eye stalk, nasal duct, gills, mouth) forming at right angles to the main body axis. We argue that the second-order divisions reflect the early pattern of cell cleavage, and that the transformation of radial and orthoradial lines into a body with sensory organs is a generic biophysical mechanism more general than the chicken embryo.

COVID-19 vaccination may cause FDG uptake beyond axillary area.

BACKGROUND: The vaccination immune response may induce false-positive 18F-FDG PET/CT uptake. CASE PRESENTATION: An extended supraclavicular lymph nodal activation after coronavirus disease 2019 (COVID-19) vaccination revealed on 18F-FDG PET/CT mimics a Virchow nodule in a patient with medical history of well-differentiated appendicular adenocarcinoma. CONCLUSION: This case highlights a nodal activation beyond axillary area and the importance of documenting vaccination history at the time of scanning to avoid false-positive results.

Effective Management of 177Lu-DOTA0-Tyr3-Octreotate Extravasation.

ABSTRACT: Radiopharmaceutical extravasation is a known nuclear medicine adverse effect, mostly with no complication in case of diagnostic radiopharmaceutical. However, a therapeutic radiopharmaceutical extravasation may have clinical consequences and must be treated quickly and effectively. We report here a case of 177Lu-DOTA0-Tyr3-octreotate extravasation.

Head-to-Head Comparison of 18F-DOPA PET/CT and 68Ga-DOTANOC PET/CT in Patients With Midgut Neuroendocrine Tumors.

PURPOSE: The aim of this study was to compare retrospectively 18F-DOPA PET/CT versus 68Ga-DOTANOC PET/CT in a group of patients affected by midgut NET. PATIENTS AND METHODS: Patients with histologically proven grade 1 or grade 2 midgut NET were explored after injection of 150 MBq of 68Ga-DOTANOC and 210 MBq of 18F-DOPA. The PET/CTs were analyzed visually and semiquantitatively at the patient level, regional level (7 defined regions), and lesion level (maximum of 5 lesions/organ). The criterion standard was determined on the basis of histology and imaging follow-up. RESULTS: Thirty patients (17 males and 13 females; median age, 63.5 years [37-82 years]) were included. Both PET/CTs were negative in 3 patients and positive in 25 patients. PET/CTs were discordant in 2 patients, with 18F-DOPA positive and 68Ga-DOTANOC negative. 18F-DOPA PET/CT detected more involved regions and more metastatic lesions than 68Ga-DOTANOC PET/CT in 6 (20%) and 10 (33.3%) patients, respectively. Of the 81 confirmed affected regions, 77 (95%) were detected by 18F-DOPA PET/CT and 71 (87.7%) by 68Ga-DOTANOC PET/CT (P < 0.0001). 18F-DOPA PET/CT detected significantly more lesions (211/221) than 68Ga-DOTANOC PET/CT (195/221), corresponding to a sensitivity of 95.5% and 88.2%, respectively (P < 0.0001). Tumor-to-background ratios were more favorable in liver for 18F-DOPA than for 68Ga-DOTANOC. Interestingly, a correlation was found between 18F-DOPA SUVmax and tumor burden and especially with the number of regions involved by the disease (P = 0.019). CONCLUSIONS: 18F-DOPA PET/CT is superior to 68Ga-DOTANOC PET/CT for the detection of lesions, and when available, this tracer may be recommended as the first-line examination for an accurate staging of midgut NET.

Incidental findings suggestive of COVID-19 in asymptomatic cancer patients undergoing 18F-FDG PET/CT in a low prevalence region.

PURPOSE: To assess the rate and pattern of incidental interstitial lung abnormalities suggestive of COVID-19 on 18F-FDG PET/CT in asymptomatic cancer patients during the period of active COVID-19 circulation between March and April 2020 in a geographic area of low prevalence of the virus. METHODS: 1396 18F-FDG PET/CT performed between January 1, 2020, and February 21, 2020, and between March 16, 2020, and April 17, 2020 for routine oncological indication were retrospectively analyzed. No patients had symptoms suggestive of COVID-19 at the time of the 18F-FDG PET/CT. Incidental interstitial pneumonias suggestive of COVID-19 were identified, and the 18F-FDG PET/CT patterns were described. We compared the incidence of these lesions in the pre-COVID and pandemic phases. RESULTS: We observed a 1.6% increase in interstitial lung abnormalities during the period of COVID-19 circulation. All had < 50% lung involvement. We describe a case series with typical and atypical interstitial pneumonias suggestive of COVID-19 as unilateral or bilateral with ground-glass opacity, consolidation, or crazy-paving patterns. CONCLUSION: The relatively low increase in incidental findings suggestive of COVID-19 infection on 18F-FDG PET/CT in asymptomatic cancer patients was in accordance with the low COVID-19 transmission in our geographic region. Nevertheless, nuclear medicine physicians should familiarize themselves with typical and atypical 18F-FDG PET/CT patterns suggestive of COVID-19 pneumonia and initiate appropriate intervention where necessary.

Does Combining Severe and Mild Cases of COVID-19 Produce Low Fatality Rates After Treatment With Hydroxychloroquine and Azithromycin?

In this issue of the Journal, Dr. Risch (Am J Epidemiol. 2020;189(11):1218-1226) posits that the use of a combination of hydroxychloroquine and azithromycin as an outpatient treatment for high-risk patients with coronavirus 19 should be increased as a way to help curtail the ongoing pandemic. However, a calculation error occurred in the original article, and new data about the studies cited have come to light. Peculiarities in the methods of data collection and reporting in those original sources must be considered when evaluating the evidence for or against hydroxychloroquine and azithromycin bitherapy.

Haute Couture or Ready-to-Wear? Tailored Pelvic Radiotherapy for Prostate Cancer Based on Individualized Sentinel Lymph Node Detection.

Prostate cancer (PCa) pelvic radiotherapy fields are defined by guidelines that do not consider individual variations in lymphatic drainage. We examined the feasibility of personalized sentinel lymph node (SLN)-based pelvic irradiation in PCa. Among a SLN study of 202 patients, we retrospectively selected 57 patients with a high risk of lymph node involvement. Each single SLN clinical target volume (CTV) was individually segmented and pelvic CTVs were contoured according to Radiation Therapy Oncology Group (RTOG) guidelines. We simulated a radiotherapy plan delivering 46 Gy and calculated the dose received by each SLN. Among a total of 332 abdominal SLNs, 305 pelvic SLNs (beyond the aortic bifurcation) were contoured (mean 5.4/patient). Based on standard guidelines, CTV missed 67 SLNs (22%), mostly at the common iliac level (40 SLNs). The mean distance between iliac vessels and the SLN was 11mm, and despite a 15mm margin around the iliac vessels, 9% of SLNs were not encompassed by the CTV. Moreover, 42 SLNs (63%) did not receive 95% of the prescribed dose. Despite a consensus on contouring guidelines, a significant proportion of SLNs were not included in the pelvic CTV and did not receive the prescribed dose. A tailored approach based on individual SLN detection would avoid underdosing pelvic lymph nodes that potentially contain tumor cells.

Initial Clinical Results of a Novel Immuno-PET Theranostic Probe in Human Epidermal Growth Factor Receptor 2-Negative Breast Cancer.

This prospective study evaluated the imaging performance of a novel pretargeting immunologic PET (immuno-PET) method in patients with human epidermal growth factor receptor 2 (HER2)-negative, carcinoembryonic antigen (CEA)-positive metastatic breast cancer, compared with CT, bone MRI, and 18F-FDG PET. Methods: Twenty-three patients underwent whole-body immuno-PET after injection of 150 MBq of 68Ga-IMP288, a histamine-succinyl-glycine peptide given after initial targeting of a trivalent anti-CEA, bispecific, antipeptide antibody. The gold standards were histology and imaging follow-up. Tumor SUVs (SUVmax and SUVmean) were measured, and tumor burden was analyzed using total tumor volume and total lesion activity. Results: The total lesion sensitivity of immuno-PET and 18F-FDG PET were 94.7% (1,116/1,178) and 89.6% (1,056/1,178), respectively. Immuno-PET had a somewhat higher sensitivity than CT or 18F-FDG PET in lymph nodes (92.4% vs. 69.7% and 89.4%, respectively) and liver metastases (97.3% vs. 92.1% and 94.8%, respectively), whereas sensitivity was lower for lung metastases (48.3% vs. 100% and 75.9%, respectively). Immuno-PET showed higher sensitivity than MRI or 18F-FDG PET for bone lesions (95.8% vs. 90.7% and 89.3%, respectively). In contrast to 18F-FDG PET, immuno-PET disclosed brain metastases. Despite equivalent tumor SUVmax, SUVmean, and total tumor volume, total lesion activity was significantly higher with immuno-PET than with 18F-FDG PET (P = 0.009). Conclusion: Immuno-PET using anti-CEA/anti-IMP288 bispecific antibody, followed by 68Ga-IMP288, is a potentially sensitive theranostic imaging method for HER2-negative, CEA-positive metastatic breast cancer patients and warrants further research.

Pretreatment 18F-FDG PET/CT Radiomics Predict Local Recurrence in Patients Treated with Stereotactic Body Radiotherapy for Early-Stage Non-Small Cell Lung Cancer: A Multicentric Study.

The aim of this retrospective multicentric study was to develop and evaluate a prognostic 18F-FDG PET/CT radiomic signature in early-stage non-small cell lung cancer patients treated with stereotactic body radiotherapy (SBRT). Methods: Patients from 3 different centers (n = 27, 29, and 8) were pooled to constitute the training set, whereas the patients from a fourth center (n = 23) were used as the testing set. The primary endpoint was local control. The primary tumor was semiautomatically delineated in the PET images using the fuzzy locally adaptive Bayesian algorithm, and manually in the low-dose CT images. In total, 184 Image Biomarkers Standardization Initiative-compliant radiomic features were extracted. Seven clinical and treatment parameters were included. We used ComBat to harmonize radiomic features extracted from the 4 institutions relying on different PET/CT scanners. In the training set, variables found significant in the univariate analysis were fed into a multivariate regression model, and models were built by combining independent prognostic factors. Results: Median follow-up was 21.1 mo (range, 1.7-63.4 mo) and 25.5 mo (range, 7.7-57.8 mo) in training and testing sets, respectively. In univariate analysis, none of the clinical variables, 2 PET features, and 2 CT features were significantly predictive of local control. The best predictive models in the training set were obtained by combining one feature from PET (Information Correlation 2) and one feature from CT (flatness), reaching a sensitivity of 100% and a specificity of 96%. Another model combining 2 PET features (Information Correlation 2 and strength) reached sensitivity of 100% and specificity of 88%, both with an undefined hazard ratio (P < 0.001). The latter model obtained an accuracy of 0.91 (sensitivity, 100%; specificity, 81%), with a hazard ratio undefined (P = 0.023) in the testing set; however, other models relying on CT radiomic features only or the combination of PET and CT features failed to validate in the testing set. Conclusion: We showed that 2 radiomic features derived from 18F-FDG PET were independently associated with local control in patients with non-small cell lung cancer undergoing SBRT and could be combined in an accurate predictive model. This model could provide local relapse-related information and could be helpful in clinical decision making.

Electrical stimulation of developmental forces reveals the mechanism of limb formation in vertebrate embryos.

Current knowledge on limbs development lacks a physical description of the forces leading to formation of the limbs precursors or "buds". Earlier stages of development are driven by large scale morphogenetic movements, such as dipolar vortical flows and mechanical buckling, pulled by rings of cells. It is a natural hypothesis that similar phenomena occur during limb formation. However it is difficult to experiment on the developmental forces, in such a complex dynamic system. Here, we report a physical study of hindlimb bud formation in the chicken embryo. We use electrical stimulation to enhance the physical forces present in the tissue, prior to limb bud formation. By triggering the physical forces in a rapid and amplified pattern, we reveal the mechanism of formation of the hindlimbs: the early presumptive embryonic territory is composed of a set of rings encased like Russian dolls. Each ring constricts in an excitable pattern of force, and the limb buds are generated by folding at a pre-existing boundary between two rings, forming the dorsal and ventral ectoderms. The amniotic sac buckles at another boundary. Physiologically, the actuator of the excitable force is the tail bud pushing posteriorly along the median axis. The developmental dynamics suggests how animals may evolve by modification of the magnitude of these forces, within a common broken symmetry. On a practical level, localized electrical stimulation of morphogenetic forces opens the way to in vivo electrical engineering of tissues.

Preliminary results of a 68 Ga-PSMA PET/CT prospective study in prostate cancer patients with occult recurrence: Diagnostic performance and impact on therapeutic decision-making.

BACKGROUND: In this prospective study (NCT03443609), we investigated the impact of 68Ga-PSMA-11 PET-CT on the treatment plan and therapeutic response obtained for patients with prostate cancer (PCa) presenting a recurrence with a low rising PSA. METHODS: One hundred thirty hormone-naive (PSA < 1.5 ng/mL) patients were enrolled. All patients received radical treatment. PET images were recorded 1 and 2 hours after injection of tracer and interpreted by two independent nuclear physicians. Six months after treatment ended, a PSA assay was requested to evaluate the therapeutic efficacy of the treatment based on PSMA results. RESULTS: Data analysis for the first 52 included patients has been completed. 68Ga-PSMA-11-positive lesions were detected in 38/52 (73.1%) patients. Ninety-four lesions were detected as follows, 53/94 in lymph nodes (56.4%), 25/94 in bone (26.6%), and 12/94 into the prostate bed (12.7%). Detection rates were 58%, 81%, and 82% for serum PSA levels lower than 0.25 ng/mL, between 0.25 to ≤ 0.69 ng/mL and 0.70 ng/mL, respectively. As a result of the PSMA PET-CT, therapeutic management changed in 38/52 patients (73.1%). Patients had undetectable serum PSA levels after treatment guided by 68Ga-PSMA-11 PET-CT results in 10/52 (19.2%) cases and with a PSA decrease of over 60% in 18/52 (34.6%) patients. CONCLUSION: Whilst our patient population presented a very low PSA level, preliminary results of the 68Ga-PSMA PET-CT study showed recurrence localization in more than half of the patients and this had a major clinical impact, as it resulted in treatment change in more than half of the patients and a significant decrease in PSA levels in a third of patients.