A Parametric Analysis of Embedded Tissue Marker Properties and Their Effect on the Accuracy of Displacement Measurements

Datasets obtained from cadaveric experimentation are broadly used in validating finite element models of head injury. Due to the complexity of such measurements in soft tissues, experimentalists have relied on tissue-embedded radiographic or sonomicrometry tracking markers to resolve tissue motion caused by impulsive loads. Dynamic coupling of markers with the surrounding tissue has been a previous concern, yet a thorough sensitivity investigation of marker influences on tissue deformation has not been broadly discussed. Technological improvements to measurement precision have bolstered confidence in acquired data, however precision is often conflated with accuracy; the inclusion of markers in the tissue may alter its natural response, resulting in a loss of accuracy associated with an altered displacement field. To gain an understanding of how marker properties may influence the measured response to impact, we prepared a set of nine marker designs using a Taguchi L9 array to investigate marker design choice sensitivity. Each of these designs was cast into a block of tissue simulant and subjected to repeated drop tests. Vertical displacement was measured and compared to the response of the neat material, which contained massless tracking markers. Medium density and medium stiffness markers yielded the least deviation from the neat material response. The results provide some design guidelines indicating the importance of maintaining marker matrix density ratio below 1.75 and marker stiffness below 1.0 MPa. These properties may minimize marker interference in tissue deformation. Overall, embedded marker properties must be considered when measuring the dynamic response of tissue.

A parametric analysis of embedded tissue marker properties and their effect on the accuracy of displacement measurements

Datasets obtained from cadaveric experimentation are broadly used in the validation of finite element models of head injury. Due to the complexity of such measurements in soft tissues, experimentalists have relied on tissue-embedded radiographic or sonomicrometry tracking markers to resolve the motion of the tissue due to impulsive loads. Dynamic coupling of markers with the surrounding tissue has been a previous concern, yet a thorough sensitivity investigation of marker influences on tissue deformation has not been broadly discussed. Technological improvements to measurement precision have bolstered confidence in acquired data, however precision is often conflated with accuracy; the inclusion of markers in the tissue may alter its natural response, resulting in a loss of accuracy associated with an altered displacement field. To gain an understanding of how marker properties may influence the measured response to impact, we prepared a set of nine marker designs using a Taguchi L9 array to investigate marker design choice sensitivity. Each of these designs was cast into a block of tissue simulant an subjected to repeated drop tests. Vertical displacement was measured and compared to the response of the neat material, which contained massless tracking markers. The best performing markers had both a medium density and medium stiffness. The results provide some design guidelines that indicate the importance of maintaining marker:matrix density ratio below 1.75 and marker stiffness below 1.0~MPa to minimize marker interference in tissue deformation. Overall, embedded marker properties must be considered when measuring the dynamic response of tissue.

Embryonic Environmental Niche Reprograms Somatic Cells to Express Pluripotency Markers and Participate in Adult Chimaeras

The phenomenon of the reprogramming of terminally differentiated cells can be achieved by various means, like somatic cell nuclear transfer, cell fusion with a pluripotent cell, or the introduction of pluripotency genes. Here, we present the evidence that somatic cells can attain the expression of pluripotency markers after their introduction into early embryos. Mouse embryonic fibroblasts introduced between blastomeres of cleaving embryos, within two days of in vitro culture, express transcription factors specific to blastocyst lineages, including pluripotency factors. Analysis of donor tissue marker DNA has revealed that the progeny of introduced cells are found in somatic tissues of foetuses and adult chimaeras, providing evidence for cell reprogramming. Analysis of ploidy has shown that in the chimaeras, the progeny of introduced cells are either diploid or tetraploid, the latter indicating cell fusion. The presence of donor DNA in diploid cells from chimaeric embryos proved that the non-fused progeny of introduced fibroblasts persisted in chimaeras, which is evidence of reprogramming by embryonic niche. When adult somatic (cumulus) cells were introduced into early cleavage embryos, the extent of integration was limited and only cell fusion-mediated reprogramming was observed. These results show that both cell fusion and cell interactions with the embryonic niche reprogrammed somatic cells towards pluripotency.

A Three-Dimensional Bioabsorbable Tissue Marker for Volume Replacement and Radiation Planning: A Multicenter Study of Surgical and Patient-Reported Outcomes for 818 Patients with Breast Cancer

Background Accurate identification of the tumor bed after breast-conserving surgery (BCS) ensures appropriate radiation to the tumor bed while minimizing normal tissue exposure. The BioZorb® three-dimensional (3D) bioabsorbable tissue marker provides a reliable target for radiation therapy (RT) planning and follow-up evaluation while serving as a scaffold to maintain breast contour. Methods After informed consent, 818 patients (826 breasts) implanted with the BioZorb® at 14 U.S. sites were enrolled in a national registry. All the patients were prospectively followed with the BioZorb® implant after BCS. The data collected at 3, 6, 12, and 24 months included all demographics, treatment parameters, and provider/patient-assessed cosmesis. Results The median follow-up period was 18.2 months (range, 0.2–53.4 months). The 30-day breast infection rate was 0.5 % of the patients (n = 4), and re-excision was performed for 8.1 % of the patients (n = 66), whereas 2.6 % of the patients (n = 21) underwent mastectomy. Two patients (0.2 %) had local recurrence. The patient-reported cosmetic outcomes at 6, 12, and 24 months were rated as good-to-excellent by 92.4 %, 90.6 %, and 87.3 % of the patients, respectively and similarly by the surgeons. The radiation oncologists reported planning of target volume (PTV) reduction for 46.2 % of the patients receiving radiation boost, with PTV reduction most commonly estimated at 30 %. Conclusions This report describes the first large multicenter study of 818 patients implanted with the BioZorb® tissue marker during BCS. Radiation oncologists found that the device yielded reduced PTVs and that both the patients and the surgeons reported good-to-excellent long-term cosmetic outcomes, with low adverse effects. The BioZorb® 3D tissue marker is a safe adjunct to BCS and may add benefits for both surgeons and radiation oncologists.

Identification of cell-type-specific marker genes from co-expression patterns in tissue samples

MotivationMarker genes, defined as genes that are expressed primarily in a single cell type, can be identified from the single cell transcriptome; however, such data are not always available for the many uses of marker genes, such as deconvolution of bulk tissue. Marker genes for a cell type, however, are highly correlated in bulk data, because their expression levels depend primarily on the proportion of that cell type in the samples. Therefore, when many tissue samples are analyzed, it is possible to identify these marker genes from the correlation pattern.ResultsTo capitalize on this pattern, we develop a new algorithm to detect marker genes by combining published information about likely marker genes with bulk transcriptome data in the form of a semi-supervised algorithm. The algorithm then exploits the correlation structure of the bulk data to refine the published marker genes by adding or removing genes from the list.Availability and implementationWe implement this method as an R package markerpen, hosted on https://github.com/yixuan/[email protected]

Postoperative Imaging Appearance of an Implantable Three-dimensional Bioabsorbable Tissue Marker After Breast Surgery: Initial Experience at a Single Institution

Objective Three-dimensional bioabsorbable tissue marker (BTM) placement during breast surgery is performed for the purpose of improved surgical cavity delineation for radiotherapy and improved cosmetic outcome. The purpose of this study is to evaluate the postsurgical imaging findings of BTM. Methods This Institutional Review Board-approved retrospective review included all patients implanted with BTM at breast surgery from January 2017 to September 2018. Demographics, tumor characteristics, imaging, and histologic findings were evaluated. Medical records were reviewed during a three-year period to evaluate for tumor recurrence. Results Ninety-seven patients had BTM implanted, of which 76 patients had imaging follow-up of at least 1 year. Of the 76 patients who had mammographic follow-up, 3 (3.9%) developed suspicious microcalcifications requiring biopsy, yielding ductal carcinoma in-situ in 2 patients and benign calcifications in 1 patient. Of 61 patients who had sonographic follow-up, 44 (72.1%) patients had complex fluid collections containing avascular, heterogeneously hyperechoic solid components, which remained stable or decreased in size over time; no recurrent tumors were found in this group. One patient (1.6%) had a vascular solid mass, which yielded recurrent papilloma. Four (6.6%) patients developed irregular hypoechoic masses at the surgical site, one of which corresponded with a developing asymmetry mammographically; biopsy yielded fibromatosis. Tissue sampling of the remaining three cases yielded invasive ductal carcinoma, fat necrosis, and radiation changes, respectively. Conclusion Accurate identification of the expected postoperative imaging appearance of BTM may prevent unnecessary biopsy. Suspicious findings necessitating biopsy are pleomorphic calcifications, developing asymmetry and vascular and irregular hypoechoic masses.

Multimodal soft tissue markers for bridging high-resolution diagnostic imaging with therapeutic intervention

Diagnostic imaging often outperforms the surgeon’s ability to identify small structures during therapeutic procedures. Smart soft tissue markers that translate the sensitivity of diagnostic imaging into optimal therapeutic intervention are therefore highly warranted. This paper presents a unique adaptable liquid soft tissue marker system based on functionalized carbohydrates (Carbo-gel). The liquid state of these markers allows for high-precision placement under image guidance using thin needles. Based on step-by-step modifications, the image features and mechanical properties of markers can be optimized to bridge diagnostic imaging and specific therapeutic interventions. The performance of Carbo-gel is demonstrated for markers that (i) have radiographic, magnetic resonance, and ultrasound visibility; (ii) are palpable and visible; and (iii) are localizable by near-infrared fluorescence and radio guidance. The study demonstrates encouraging proof of concept for the liquid marker system as a well-tolerated multimodal imaging marker that can improve image-guided radiotherapy and surgical interventions, including robotic surgery.