About

Dr. Marie Muller is a professor in the Department of Mechanical and Aerospace Engineering at NC State University. Her research focuses on medical ultrasound and ultrasound propagation in complex media. Her long-term objective is to advance the state-of-the-art of medical ultrasound and contribute to screening and prevention methods. Her research involves developing non-invasive methods to quantitatively characterize the microstructure of biological media such as lung and bone, leading to new technologies for diagnosing and monitoring conditions like osteoporosis, pulmonary fibrosis, and pulmonary edema. Her work attracts students due to its high societal impact, involving both theoretical and experimental methods, and fostering teamwork and collaborations with physicians, physicists, and engineers. Her multidisciplinary research provides students with opportunities to tailor their graduate experience to their interests. Outside of her professional pursuits, she enjoys family, friends, music, and food.

Research topics

• Medicine
• Radiology
• Biology
• Pathology
• Internal medicine
• Optics
• Dermatology
• Biomedical engineering
• Materials science
• Physics
• Law
• Medical physics
• Surgery
• Pediatrics
• Nuclear medicine

Selected publications

• Treprostinil Iontophoresis in Diabetic Foot Ulcers: A Single Ascending Dose Safety Study

  Fundamental and Clinical Pharmacology · 2025-11-18 · 1 citations

  articleOpen access

  ABSTRACT Background Diabetic foot ulcers (DFUs) represent a serious public health problem associated with significant morbidity and health costs. Despite optimal etiologic treatment and local care, amputation is frequent, stressing the need for new treatments. The benefit of systemic administration of vasodilators, such as prostacyclin analogues, has proven efficacy in other types of skin ulcers, but it is counterbalanced by potentially serious vasodilation‐induced, concentration‐dependent, adverse effects. Experimental data has shown the feasibility of local administration of treprostinil on the wound using iontophoresis. Objective We aimed to assess the safety of the local iontophoretic administration of treprostinil in patients with DFU through a single ascending dose safety study. Methods We conducted a prospective single ascending dose phase I study. Patients received a single dose of treprostinil applied via iontophoresis at a current density of 0.2 mA/cm 2 for 30 min. Local and systemic adverse effects were monitored, and plasma treprostinil concentrations were measured over an 8‐h follow‐up period. Results Four patients were included, and received single doses of 0.025, 0.05, 0.1, and 0.25 mg/L at 0.2 mA/cm 2 during 30 min, and were followed‐up for 8 h. All patients did not present any significant adverse effect. Plasma concentration was below < 1.8 ng/mL 8 h after the administration. Conclusions Our results suggest that iontophoresis of treprostinil is a safe procedure at 0.25 mg/mL, without systemic adverse effect, suggesting its potential as a targeted treatment for DFUs.

  PublisherOA PDFDOI

• French recommendations on multi-gene panel testing in renal cell carcinoma

  European Journal of Medical Genetics · 2025-11-20

  articleOpen access

  INTRODUCTION: Renal cancers are inherited in about 5 % of cases and are associated with several genetic syndromes. Genetic testing is recommended for selected patients suspected of having hereditary syndromes. In the absence of guidelines regarding which genes should be included for carrying out genetic screening of these individuals, discrepancies existed among the next generation sequencing (NGS) multi-gene panels (MGP) used in French laboratories. There was therefore a clear need to standardise practices and offer patients with renal cancer a consensus-based genetic testing in France. METHODS: A working group comprising national experts from the French Genetic and Cancer Group Unicancer (GGC) and from the French network on Hereditary PREDIspositions to Renal Cancer (PREDIR) and encompassing medical geneticists, genetic counsellor, molecular biologists and epidemiologists was established. The objective was to define a list of clinically relevant genes that should be included in a "GGC-PREDIR" approved NGS MGP for patients with renal cancer. A list of 32 genes of interest was compiled following an exhaustive and critical review of the literature. The inclusion or exclusion of each gene was determined based on available data regarding risk, prevalence and analyses published from large studies of patients. RESULTS: The French group of experts defined a list of 12 genes of clinical and genetic counselling relevance comprising BAP1, FH, FLCN, MET, PTEN, SDHA, SDHB, SDHC, SDHD, TSC1, TSC2 and VHL to be included in the national recommended "renal cancer" NGS MGP. For each of these genes, recommendations for renal surveillance are proposed. CONCLUSION: Unlike hereditary predisposition to breast or colon cancer, hereditary renal cancer predispositions are rare syndromes and risk estimates are lacking for most of them. Prospective studies are needed to improve our knowledge. The GGC-PREDIR experts retained 12 genes for inclusion in the NGS MGP for renal cancer patients. However, the panel will be expanded on the basis of regularly updated data from the medical literature.

  PublisherDOI

• Publisher Correction: Functional synapses between neurons and small cell lung cancer

  Nature · 2025-09-19 · 1 citations

  articleOpen access
  PublisherOA PDFDOI

• Comparison of diffusion coefficient measurement through Coherent or Incoherent Backscattering measurement, for the characterization of complex media

  The Journal of the Acoustical Society of America · 2025-04-01

  articleSenior author

  This study compares methods to calculate the diffusion coefficient (D) in complex media using Coherent or Incoherent Backscattering (CBS and IBS). In heterogeneous media like lung or bone tissue, conventional ultrasound imaging is inadequate for diagnostics. Quantitative Ultrasound (QUS), including D measurement, offers insights into the “randomness” of such media. Changes in D reflect multiple scattering effects and are associated with an increased intensity of IBS and a reduced intensity of CBS over time. The study evaluates D measurement methods with varying air inclusion proportions in soft tissues, both numerically and experimentally. The three approaches include: (1) traditional CBS with plane wave beamforming for emission and reception, (2) enhanced CBS (eCBS), which leverages phase coherence between backscattered waves in different directions to improve CBS measurements through amplitude and phase data, and (3) IBS analysis through matrix treatment to separate the incoherent intensity from the CBS peak using a virtual antireciprocity. Numerical simulations demonstrate that eCBS provides more stable and accurate diffusion measurements compared to CBS or IBS. Pending experiments on water-filled sponge phantoms and rat lungs with fibrosis seem to confirm the reliability of eCBS. This method holds promise for improved diagnostics in complex media, particularly where conventional imaging is insufficient.

  PublisherDOI

• Metastatic esophageal squamous cell carcinoma: which treatments in clinical practice?

  Hépato-Gastro & Oncologie Digestive · 2025-03-01

  article1st authorCorresponding
  PublisherDOI

• Efficacy of immunotherapy in gastrointestinal (GI) tumors with mismatch repair deficient (MMRd) unusual phenotype: an AGEO real-world study

  Journal for ImmunoTherapy of Cancer · 2025-10-01 · 3 citations

  articleOpen access

  Background Tumors with mismatch repair deficiency (MMRd) classically display concomitant loss of MLH1/PMS2 or MSH2/MSH6 on immunohistochemistry (IHC) with microsatellite instability-high (MSI-High) status on molecular testing. Nevertheless, a different phenotype can occur in up to 15% of MMRd tumors (unusual phenotype). Data on the efficacy of immunotherapy in this population remain scarce. Methods We conducted a retrospective study within the IMMUNODIG MSI cohort including patients with advanced gastrointestinal MMRd tumors treated with immune checkpoint blockade in the real-world setting. We selected patients with both IHC and MSI assays data available. Unusual MMRd tumors were classified into four distinct groups: (1) isolated loss of PMS2 or MSH6 with MSI-H (isolated/MSI-H), (2) complex loss of MMR proteins with MSI-H (complex/MSI-H), (3) loss of one or more MMR proteins without MSI-H (MMRd-IHC/microsatellite stability (MSS) or MSI-low (MSI-L)), and (4) four MMR proteins retained with MSI-H (retained IHC/MSI-H). Results Out of 759 patients in the IMMUNODIG-MSI cohort, 571 patients met inclusion criteria. Of these, 90 (15.8%) had an unusual phenotype (47 isolated/MSI-H, 19 complex/MSI-H, 16 MMRd-IHC/MSS or MSI-L and 8 retained IHC/MSI-H). Compared with classical phenotypes, patients with a tumor harboring an unusual phenotype had a younger age at treatment (p=0.005), increased RAS mutation (p=0.005), reduced BRAF p.V600E mutation rates (p<0.001), a higher proportion of Lynch syndrome (p<0.001) and a higher prevalence of non-colorectal cancers (p=0.021). After a median follow-up of 28.1 months (mo), there was a significant difference in progression-free survival, with median values of not reached, 66.4 mo, 37.2 mo, 18.3 mo and 5.5 mo for complex/MSI-H, isolated/MSI-H, classical, retained IHC/MSI-H and MMRd-IHC/MSS or MSI-L subgroups, respectively (p<0.001). Notably, objective response rates were 59.1%, 58.7%, and 63.2% for complex/MSI-H, isolated/MSI-H and classical contrasting with 50% and 25% for retained IHC/MSI-H and MMRd-IHC/MSS or MSI-L, with no complete response observed in the latter two. Conclusion Our findings underscore the need for dual testing and advocate for the presence of both MMRd-IHC and MSI-H for optimal immunotherapy response. Of note, complex MMR aberrations and isolated PMS2/MSH6 losses with MSI-H may represent promising candidates for enhanced immunotherapy efficacy.

  PublisherOA PDFDOI

• Estimating vascular density by using quantitative ultrasound in microbubble enhanced vessel networks

  The Journal of the Acoustical Society of America · 2025-04-01

  articleSenior author

  This study investigates the use of quantitative ultrasound techniques for characterizing tumor-related angiogenesis. Neo-vessel density serves as an established biomarker of breast cancer malignancy, making it crucial to develop methods for its quantification. Our approach involves analyzing scattering from ultrasound contrast agents within vascular networks. We assess whether parameters derived from plane wave imaging and full synthetic aperture data acquisition effectively estimate vessel density. Healthy rat kidneys were used as a model for vascular networks. Following anesthesia, microbubbles were injected through the tail vein at an infusion rate of 1.5e8 bubbles/min. Ultrasound data acquisition was performed using a Verasonics L-11-5v linear array transducer connected to a Verasonics 256 Vantage NXT scanner. A full synthetic aperture approach was applied, utilizing all 128 transducer elements to transmit two-cycle Gaussian pulses at a central frequency of 7.6 MHz. Backscattered signals were recorded across all elements, producing a 3-D Inter-Element Response Matrix (IRM). The Diffusion constant and multiple scattering-related parameters were calculated by separating coherent and incoherent backscattered intensities and analyzing the temporal growth of the diffusive halo. Acoustic angiography images were used for comparison, and light sheet imaging served as the ground truth for validating vascular density measurements.

  PublisherDOI

• Treatments of HER2-positive oesogastric adenocarcinoma

  Hépato-Gastro & Oncologie Digestive · 2025-01-01

  article1st authorCorresponding
  PublisherDOI

• Functional synapses between neurons and small cell lung cancer

  Nature · 2025-09-10 · 32 citations

  articleOpen access

  Abstract Small cell lung cancer (SCLC) is a highly aggressive type of lung cancer, characterized by rapid proliferation, early metastatic spread, frequent early relapse and a high mortality rate 1–3 . Recent evidence has suggested that innervation has an important role in the development and progression of several types of cancer 4,5 . Cancer-to-neuron synapses have been reported in gliomas 6,7 , but whether peripheral tumours can form such structures is unknown. Here we show that SCLC cells can form functional synapses and receive synaptic transmission. Using in vivo insertional mutagenesis screening in conjunction with cross-species genomic and transcriptomic validation, we identified neuronal, synaptic and glutamatergic signalling gene sets in mouse and human SCLC. Further experiments revealed the ability of SCLC cells to form synaptic structures with neurons in vitro and in vivo. Electrophysiology and optogenetic experiments confirmed that cancer cells can receive NMDA receptor- and GABA A receptor-mediated synaptic inputs. Fitting with a potential oncogenic role of neuron–SCLC interactions, we showed that SCLC cells derive a proliferation advantage when co-cultured with vagal sensory or cortical neurons. Moreover, inhibition of glutamate signalling had therapeutic efficacy in an autochthonous mouse model of SCLC. Therefore, following malignant transformation, SCLC cells seem to hijack synaptic signalling to promote tumour growth, thereby exposing a new route for therapeutic intervention.

  PublisherOA PDFDOI

• Characterizing random complex biological media by quantifying ultrasound multiple scattering

  UNC Libraries · 2025-05-02

  articleOpen access

  Introduction: In this in silico, in vitro, and in vivo study, we propose metrics for the characterization of highly scattering media using backscattered acoustic waves in the MHz range, for application to the characterization of biological media. Methods: Multi-element array transducers are used to record the ultrasonic Inter element Response Matrix (IRM) of scattering phantoms and of lung tissue in rodent models of pulmonary fibrosis. The distribution of singular values of the IRM in the frequency domain is then studied to quantify the multiple scattering contribution. Numerical models of scattering media, as well as gelatin-glass bead and polydimethylsiloxane phantoms with different scatterer densities, are used as a first step to demonstrate the proof of concept. Results: The results show that changes in microstructure of a complex random medium affect parameters associated with the distribution of singular values. Two metrics are proposed: E ( X ) , which is the expected value of the singular value distribution, and λ max , the maximum value of the probability density function of the singular value distribution, i.e., the most represented singular value. After validation of the methods in silico and in phantoms, we show that these metrics are relevant to evaluate pulmonary fibrosis in an in vivo rodent study on six control rats and eighteen rats with varying degrees of severity of pulmonary fibrosis. In rats, a moderate correlation was found between the severity of pulmonary fibrosis and metrics E ( X ) and λ max . Discussion: These results suggest that such parameters could be used as metrics to estimate the amount of multiple scattering in highly heterogeneous media, and that these parameters could contribute to the evaluation of structural changes in lung microstructure.

  PublisherDOI

Recent grants

• Novel Ultrasound Localization of Pulmonary Nodules during Video Assisted Thoracic Surgery to Improve Surgical Resection

  NIH · $362k · 2019–2022

• Ultrasonic characterization of atherosclerotic plaque using multiple scattering

  NIH · $140k · 2016–2019

• Assessment of bone micro-structure using ultrasonic methods

  NIH · $139k · 2016–2019

• Ultrasound enhanced platelet-like particle therapy for accelerated wound repair

  NIH · $343k · 2017–2020

Frequent coauthors

• Emmanuel Bossy

  Centre National de la Recherche Scientifique

  195 shared

• Arnaud Derode

  Institut Langevin

  166 shared

• Fabien Mézière

  Centre National de la Recherche Scientifique

  156 shared

• Mickaël Tanter

  Inserm

  133 shared

• Jean‐Luc Gennisson

  Commissariat à l'Énergie Atomique et aux Énergies Alternatives

  107 shared

• Thomas M. Egan

  Topcon (Netherlands)

  75 shared

• John Blackwell

  69 shared

• Maryline Talmant

  Sorbonne Université

  68 shared

Education

• PhD, Physics

  Université Paris Diderot

  2006