Chantal Pauli

Weill Cornell Medical College, New York, New York, United States

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Publications (33)167.31 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Objectives: To determine T2* relaxation in articular cartilage using ultrashort echo time (UTE) imaging and bi-component analysis, with an emphasis on the deep radial and calcified cartilage. Methods: Ten patellar samples were imaged using two-dimensional (2D) UTE and Car-Purcell-Meiboom-Gill (CPMG) sequences. UTE images were fitted with a bi-component model to calculate T2* and relative fractions. CPMG images were fitted with a single-component model to calculate T2. The high signal line above the subchondral bone was regarded as the deep radial and calcified cartilage. Depth and orientation dependence of T2*, fraction and T2 were analyzed with histopathology and polarized light microscopy, confirming normal regions of articular cartilage. An interleaved multi-echo UTE acquisition scheme was proposed for in vivo applications (n=5). Results: The short T2* values remained relatively constant across the cartilage depth while the long T2* values and long T2* fractions tended to increase from subchondral bone to the superficial cartilage. Long T2*s and T2s showed significant magic angle effect for all layers of cartilage from the medial to lateral facets, while the short T2* values and T2* fractions are insensitive to the magic angle effect. The deep radial and calcified cartilage showed a mean short T2* of 0.80±0.05 ms and short T2* fraction of 39.93±3.05% in vitro, and a mean short T2* of 0.93±0.58 ms and short T2* fraction of 35.03±4.09% in vivo. Conclusion: UTE bi-component analysis can characterize the short and long T2* values and fractions across the cartilage depth, including the deep radial and calcified cartilage. The short T2* values and T2* fractions are magic angle insensitive.
    Osteoarthritis and Cartilage 09/2015; DOI:10.1016/j.joca.2015.08.017 · 4.17 Impact Factor

  • Cancer Research 08/2015; 75(15 Supplement):4672-4672. DOI:10.1158/1538-7445.AM2015-4672 · 9.33 Impact Factor

  • Cancer Research 08/2015; 75(15 Supplement):4745-4745. DOI:10.1158/1538-7445.AM2015-4745 · 9.33 Impact Factor

  • Cancer Research 08/2015; 75(15 Supplement):5269-5269. DOI:10.1158/1538-7445.AM2015-5269 · 9.33 Impact Factor

  • Cancer Research 08/2015; 75(15 Supplement):3880-3880. DOI:10.1158/1538-7445.AM2015-3880 · 9.33 Impact Factor
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    ABSTRACT: Understanding molecular mechanisms of response and resistance to anticancer therapies requires prospective patient follow-up and clinical and functional validation of both common and low-frequency mutations. We describe a whole-exome sequencing (WES) precision medicine trial focused on patients with advanced cancer. To understand how WES data affect therapeutic decision making in patients with advanced cancer and to identify novel biomarkers of response. Patients with metastatic and treatment-resistant cancer were prospectively enrolled at a single academic center for paired metastatic tumor and normal tissue WES during a 19-month period (February 2013 through September 2014). A comprehensive computational pipeline was used to detect point mutations, indels, and copy number alterations. Mutations were categorized as category 1, 2, or 3 on the basis of actionability; clinical reports were generated and discussed in precision tumor board. Patients were observed for 7 to 25 months for correlation of molecular information with clinical response. Feasibility, use of WES for decision making, and identification of novel biomarkers. A total of 154 tumor-normal pairs from 97 patients with a range of metastatic cancers were sequenced, with a mean coverage of 95X and 16 somatic alterations detected per patient. In total, 16 mutations were category 1 (targeted therapy available), 98 were category 2 (biologically relevant), and 1474 were category 3 (unknown significance). Overall, WES provided informative results in 91 cases (94%), including alterations for which there is an approved drug, there are therapies in clinical or preclinical development, or they are considered drivers and potentially actionable (category 1-2); however, treatment was guided in only 5 patients (5%) on the basis of these recommendations because of access to clinical trials and/or off-label use of drugs. Among unexpected findings, a patient with prostate cancer with exceptional response to treatment was identified who harbored a somatic hemizygous deletion of the DNA repair gene FANCA and putative partial loss of function of the second allele through germline missense variant. Follow-up experiments established that loss of FANCA function was associated with platinum hypersensitivity both in vitro and in patient-derived xenografts, thus providing biologic rationale and functional evidence for his extreme clinical response. The majority of advanced, treatment-resistant tumors across tumor types harbor biologically informative alterations. The establishment of a clinical trial for WES of metastatic tumors with prospective follow-up of patients can help identify candidate predictive biomarkers of response.
    07/2015; 1(4):466-474. DOI:10.1001/jamaoncol.2015.1313
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    ABSTRACT: Primary bone cancers are among the deadliest cancer types in adolescents, with osteosarcomas being the most prevalent form. Osteosarcomas are commonly treated with multi-drug neoadjuvant chemotherapy and therapy success as well as patient survival is affected by the presence of tumor suppressors. In order to assess the prognostic value of tumor-suppressive biomarkers, primary osteosarcoma tissues were analyzed prior to and after neoadjuvant chemotherapy. We constructed a tissue microarray from high grade osteosarcoma samples, consisting of 48 chemotherapy naïve biopsies (BXs) and 47 tumor resections (RXs) after neoadjuvant chemotherapy. We performed immunohistochemical stainings of P53, P16, maspin, PTEN, BMI1 and Ki67, characterized the subcellular localization and related staining outcome with chemotherapy response and overall survival. Binary logistic regression analysis was used to analyze chemotherapy response and Kaplan-Meier-analysis as well as the Cox proportional hazards model was applied for analysis of patient survival. No significant associations between biomarker expression in BXs and patient survival or chemotherapy response were detected. In univariate analysis, positive immunohistochemistry of P53 (P = 0.008) and P16 (P16; P = 0.033) in RXs was significantly associated with poor survival prognosis. In addition, presence of P16 in RXs was associated with poor survival in multivariate regression analysis (P = 0.003; HR = 0.067) while absence of P16 was associated with good chemotherapy response (P = 0.004; OR = 74.076). Presence of PTEN on tumor RXs was significantly associated with an improved survival prognosis (P = 0.022). Positive immunohistochemistry (IHC) of P16 and P53 in RXs was indicative for poor overall patient survival whereas positive IHC of PTEN was prognostic for good overall patient survival. In addition, we found that P16 might be a marker of osteosarcoma chemotherapy resistance. Therefore, our study supports the use of tumor RXs to assess the prognostic value of biomarkers.
    BMC Cancer 05/2015; 15(1):379. DOI:10.1186/s12885-015-1397-4 · 3.36 Impact Factor

  • Nature 04/2015; 520(7547):E11-2. DOI:10.1038/nature14265 · 41.46 Impact Factor
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    ABSTRACT: the aim of this pilot study was to implement ultrashort echo time (UTE) MRI with bi-component analysis on grossly normal Achilles tendons with histologic correlation. six tendon samples which were grossly normal on visual inspection and palpation were harvested. A 2D UTE pulse sequence was implemented on a 3T MR scanner and bi-component and single-component T2* analysis was performed. Tendon samples were histologically processed and evaluated. mean short T2* fraction was 79.2% (95% confidence interval [CI], 70.1 - 88.3%), mean short T2* was 1.8 ms (95% CI, 1.3 - 2.3 ms), mean long T2* fraction was 20.8% (95% CI, 11.7 - 29.9%), mean long T2* was 9.2 ms (95% CI, 5.1 - 13.3 ms), and mean single-component T2* was 2.5 ms (95% CI, 1.8 - 3.1 ms). 2D UTE MRI with bi-component and single-component T2* analysis was successfully implemented. Inter-individual variation can be demonstrated in grossly and histologically normal Achilles tendons.
    Muscles 04/2015; 5(2):58-62. DOI:10.11138/mltj/2015.5.2.058
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    ABSTRACT: Background To determine if off-saturation ratio (OSR) measured with the ultrashort echo time magnetization transfer (UTE-MT) sequence could differentiate between tendons under different states of tensile load and to compare these changes between normal versus degenerated tendons.Methods Fourteen tendons were imaged at 3 Tesla before and during the application of 0.5–1 kg tension. A two-dimensional (2D) -UTE-MT sequence with 1.5, 3, and 5 kHz frequency offsets was used on nine tendons and a 3D-UTE-MT sequence with 1.5 kHz frequency offset was used on five tendons. OSR was calculated and compared for each condition. Histologic correlation was performed using light microscopy.ResultsIn general, OSR increased after the application of tension. Mean increase of 2D OSR was 0.035 (95% confidence interval [CI], 0.013–0.056) at 1.5 kHz offset (P < 0.01), 0.031 (95% CI, 0.023–0.040) at 3 kHz offset (P < 0.01), and 0.013 (95% CI, −0.013–0.027) at 5 kHz offset (P = 0.07) from pre- to posttension states. Mean increase of 3D OSR was 0.026 (95% CI, 0.008–0.044) at a 1.5 kHz offset (P = 0.02) from pre- to posttension states. Mean decrease of 2D OSR at 1.5 kHz offset was 0.074–0.087 when comparing normal versus degenerated tendons (P < 0.01).ConclusionOSR as measured with 2D or 3D UTE-MT sequences can detect the changes in hydration seen when tendons are placed under two different states of tensile load, but these changes are smaller than those encountered when comparing between normal versus pathologic tendons. Lower off-resonance saturation frequencies (3 kHz or less) are more sensitive to these changes than higher off-resonance saturation frequencies.J. Magn. Reson. Imaging 2015.
    Journal of Magnetic Resonance Imaging 03/2015; 42(4). DOI:10.1002/jmri.24881 · 3.21 Impact Factor

  • 104th Annual Meeting of the; 02/2015
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    ABSTRACT: Objectives: To analyze the correlation of computed tomography (CT) perfusion parameters blood flow (BF), blood volume (BV), and mean transit time (MTT) with presurgical prostate cancer data. Methods: Ninety-eight patients with biopsy-proven prostate cancer underwent a CT-perfusion scan of the prostate. MTT, BF, and BV were determined and correlated with prostate-specific antigen (PSA) level, tumor load and Gleason score of transrectal ultrasonography-guided biopsy specimens. Results: Mean BF was 41.3 ml/100 ml*min(-1), BV 5.2 ml/100 ml, MTT 8.7 s. Moderate correlations were observed between Gleason score and BF (0.35) and between PSA and BF (0.33) and BV (0.30). Conclusions: CT-perfusion shows no valuable correlation with presurgical prostate cancer data.
    Clinical Imaging 08/2014; 38(6). DOI:10.1016/j.clinimag.2014.07.011 · 0.81 Impact Factor
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    ABSTRACT: Many studies in the field of cell-based cartilage repair have focused on identifying markers associated with the differentiation status of human articular chondrocytes (HAC) that could predict their chondrogenic potency. A previous study from our group showed a correlation between the expression of S100 protein in HAC and their chondrogenic potential. The aims of the current study were to clarify which S100 proteins are associated with HAC differentiation status and to provide an S100-based assay for measuring HAC chondrogenic potential. The expression patterns of S100A1 and S100B were investigated in cartilage and in HAC cultured under conditions promoting dedifferentiation (monolayer culture) or redifferentiation (pellet culture or BMP4 treatment in monolayer culture), using characterized antibodies specifically recognizing S100A1 and S100B, by immunohistochemistry, immunocytochemistry, Western blot, and gene expression analysis. S100A1 and S100B were expressed homogeneously in all cartilage zones, and decreased during dedifferentiation. S100A1, but not S100B, was re-expressed in pellets and co-localized with collagen II. Gene expression analysis revealed concomitant modulation of S100A1, S100B, collagen type II, and aggrecan: down-regulation during monolayer culture and up-regulation upon BMP4 treatment. These results strongly support an association of S100A1, and to a lesser extent S100B, with the HAC differentiated phenotype. To facilitate their potential application, we established an S100A1/B-based flow cytometry assay for accurate assessment of HAC differentiation status. We propose S100A1 and S100B expression as a marker to develop potency assays for cartilage regeneration cell therapies, and as a redifferentiation readout in monolayer cultures aiming to investigate stimuli for chondrogenic induction. J. Cell. Physiol. © 2014 Wiley Periodicals, Inc.
    Journal of Cellular Physiology 08/2014; 229(8). DOI:10.1002/jcp.24547 · 3.84 Impact Factor
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    ABSTRACT: The aim of this study was to assess the performance of dynamic contrast-enhanced computed tomography of the prostate in patients with biopsy-proven prostate cancer. A total of 46 male patients (median age, 65 years; range, 49-73 years) with biopsy-proven prostate cancer underwent an en bloc computed tomography perfusion (CTP) scan of the prostate before surgery. The perfusion parameters mean transit time (MTT), blood flow (BF), and blood volume (BV), as well as the microvessel density (MVD) of surgical specimens were determined. Differences in CTP parameters and MVD among postsurgical Gleason score (sGS) and postsurgical combined Gleason grade (sGG) groups were analyzed. Spearman correlation coefficients were determined between CTP parameters and presurgical biopsy-derived Gleason score (bGS), presurgical biopsy-derived combined Gleason grade, sGS, sGG, MVD, and pathological tumor stage. A linear regression analysis was carried out for exogenous variables BF, BV, MTT, bGS, and presurgical biopsy-derived combined Gleason grade and endogenous variables sGS, sGG, MVD, and T stage. A receiver operating characteristics analysis was performed to analyze the discriminating performance of CTP parameters and bGS between intermediate- and high-grade tumors. The mean perfusion parameters within the prostate tissue were as follows: BF, 39.1 ± 13.4 mL/100 mL min; BV, 4.9 ± 2.4 mL/100 mL; and MTT, 8.9 ± 3.7 seconds. The mean MVD of the tumor tissue was 144.3 ± 55.6/mm. Computed tomography perfusion parameters and MVD were significantly higher in patients with high-grade tumors compared with those with intermediate-grade tumors (P < 0.01 for BF, BV, and MVD). Only BV and MVD were significantly different among sGS and sGG groups. Moderate correlations were found between BF and sGS (0.38) and between BV and sGS (0.43). Linear relations of BV to sGS and to sGG were found. Blood volume (area under the curve, 0.86) was superior to bGS (area under the curve, 0.75) in discriminating high-grade from intermediate-grade tumors. Computed tomography perfusion parameters derived by en bloc perfusion of the prostate are higher in high-grade tumors compared with intermediate-grade tumors. Blood flow and BV correlate with the definitive Gleason score. Blood volume predicts high-grade tumors better than does the Gleason score of biopsy specimens. Further studies are needed to determine a potential role for CTP in prostate cancer patients.
    Investigative radiology 04/2014; 49(9). DOI:10.1097/RLI.0000000000000055 · 4.44 Impact Factor
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    ABSTRACT: The purpose of this study is to assess the relationship of CT-perfusion (CTP), 18F-FDG-PET/CT and histological parameters, and the possible added value of CTP to FDG-PET/CT in the initial staging of lung cancer. Fifty-four consecutive patients (median age 65 years, 15 females, 39 males) with suspected lung cancer were evaluated prospectively by CT-perfusion scan and 18F-FDG-PET/CT scan. Overall, 46 tumors were identified. CTP parameters blood flow (BF), blood volume (BV), and mean transit time (MTT) of the tumor tissue were calculated. Intratumoral microvessel density (MVD) was assessed quantitatively. Differences in CTP parameters concerning tumor type, location, PET positivity of lymph nodes, TNM status, and UICC stage were analyzed. Spearman correlation analyses between CTP and 18F-FDG-PET/CT parameters (SUVmax, SUVmean, PETvol, and TLG), MVD, tumor size, and tumor stage were performed. The mean BF (mL/100 mL min-1), BV (mL/100 mL), and MTT (s) was 35.5, 8.4, and 14.2, respectively. The BF and BV were lower in tumors with PET-positive lymph nodes (p = 0.02). However, the CTP values were not significantly different among the N stages. The CTP values were not different, depending on tumor size and location. No significant correlation was found between CTP parameters and MVD. Overall, the CTP information showed only little additional information for the initial staging compared with standard FDG-PET/CT. Low perfusion in lung tumors might possibly be associated with metabolically active regional lymph nodes. Apart from that, both CTP and 18F-FDG-PET/CT parameter sets may reflect different pathophysiological mechanisms in lung cancer.
    EJNMMI Research 01/2014; 4(1):6. DOI:10.1186/2191-219X-4-6
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    ABSTRACT: Aneurysmal bone cyst (ABC), once considered a reactive lesion, has been proven to be a neoplasia characterized by rearrangements of the USP6-gene. Aggressive local growth and recurrences are common and therapeutic options may be limited due to the vicinity of crucial structures. We describe a case of a locally aggressive, multinucleated giant cell-containing lesion of the forearm of a 21-year old woman, treated with denosumab for recurrent, surgically uncontrollable disease. Under the influence of this RANKL inhibitor, the tumor showed a marked reduction of the content of the osteoclastic giant cells and an extensive metaplastic osteoid production leading to the bony containment, mostly located intracortically in the proximal radius. The diagnosis of a periosteal ABC was confirmed by FISH demonstrating USP6 gene rearrangement on the initial biopsy. Function conserving surgery could be performed, enabling reconstruction of the affected bone. Inhibition of RANKL with denosumab may offer therapeutic option for patients not only with giant cell tumors but also with ABCs.
    World Journal of Surgical Oncology 01/2014; 12(1):17. DOI:10.1186/1477-7819-12-17 · 1.41 Impact Factor
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    ABSTRACT: To identify novel genes and pathways specific to the superficial zone (SZ), middle zone (MZ), and deep zone (DZ) of normal articular cartilage. Articular cartilage was obtained from the knees of 4 normal human donors. The cartilage zones were dissected on a microtome. RNA was analyzed on human genome arrays. The zone-specific DNA array data obtained from human tissue were compared to array data obtained from bovine cartilage. Genes differentially expressed between zones were evaluated using direct annotation for structural or functional features, and by enrichment analysis for integrated pathways or functions. The greatest differences in genome-wide RNA expression data were between the SZ and DZ in both human and bovine cartilage. The MZ, being a transitional zone between the SZ and DZ, thereby shared some of the same pathways as well as structural/functional features of the adjacent zones. Cellular functions and biologic processes that were enriched in the SZ relative to the DZ included, most prominently, extracellular matrix–receptor interactions, cell adhesion molecule functions, regulation of actin cytoskeleton, ribosome-related functions, and signaling aspects such as the IFN, IL4, Cdc42/Rac, and JAK/STAT signaling pathways. Two pathways were enriched in the DZ relative to the SZ, including PPARG and EGFR/SMRTE. These differences in cartilage zonal gene expression identify new markers and pathways that govern the unique differentiation status of chondrocyte subpopulations.
    Arthritis & Rheumatology 02/2013; 65(2). DOI:10.1002/art.37760 · 7.76 Impact Factor

  • Journal of thoracic oncology: official publication of the International Association for the Study of Lung Cancer 06/2012; 7(10):e23-4. DOI:10.1097/JTO.0b013e3182629903 · 5.28 Impact Factor
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    ABSTRACT: To correlate short and long T2* water fractions, derived from ultrashort-echo time (TE) magnetic resonance (MR) imaging, with semiquantitative histopathologic and polarized light microscopic (PLM) assessment of human cadaveric patellae cartilage. Twenty human cadaveric patellae were evaluated by using ultrashort-TE imaging, spin-echo imaging, histopathologic analysis, and PLM, with institutional review board approval. Short and long T2* water components were evaluated for each patella by using bicomponent fitting of ultrashort-TE signal decay. Four to six regions of interest (ROIs) within each patella were chosen for correlation between ultrashort-TE bicomponent analysis, histopathologic grading (Mankin score), and PLM grading (Vaudey score). Ultrashort-TE imaging with bicomponent analysis showed two distinct water components with a short T2* and a longer T2* in all patellae. ROI analysis showed that the short T2* fraction was correlated significantly with the Mankin (ρ = 0.66, P < .001) and Vaudey (ρ = 0.68, P < .001) scores. The Mankin scores were weakly positively correlated with T2 (ρ = 0.28, P = .13) and short T2* (ρ = 0.24, P = .14) but were negatively correlated with long T2* (ρ = -0.55, P < .01). The Vaudey scores were weakly positively correlated with T2 (ρ = 0.18, P = .16) and short T2* (ρ = 0.22, P = .14) but were negatively correlated with long T2* (ρ = -0.55, P < .01). Short T2* water fraction derived from ultrashort-TE imaging with bicomponent analysis correlates significantly with both the Mankin and Vaudey scores and may serve as a biomarker of cartilage degeneration.
    Radiology 05/2012; 264(2):484-93. DOI:10.1148/radiol.12111883 · 6.87 Impact Factor

Publication Stats

230 Citations
167.31 Total Impact Points


  • 2015
    • Weill Cornell Medical College
      New York, New York, United States
  • 2014
    • University of Zurich
      Zürich, Zurich, Switzerland
  • 2011-2013
    • The Scripps Research Institute
      • Department of Molecular and Experimental Medicine
      La Jolla, California, United States
    • Gulhane Military Medical Academy
      • Department of Radiology
      Ankara, Ankara, Turkey
  • 2012
    • Luzerner Kantonsspital
      Luzern, Lucerne, Switzerland