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Introduction: To minimize the risk of local tumor progression after thermal ablation of liver malignancies, complete tumor ablation with sufficient ablation margins is a prerequisite. This has resulted in ablation margin quantification to become a rapidly evolving field. The aim of this systematic review is to give an overview of the available literature with respect to clinical studies and technical aspects potentially influencing the interpretation and evaluation of ablation margins. Methods: The Medline database was reviewed for studies on radiofrequency and microwave ablation of liver cancer, ablation margins, image processing and tissue shrinkage. Studies included in this systematic review were analyzed for qualitative and quantitative assessment methods of ablation margins, segmentation and co-registration methods, and the potential influence of tissue shrinkage occurring during thermal ablation. Results: 75 articles were included of which 58 were clinical studies. In most clinical studies the aimed minimal ablation margin (MAM) was ≥ 5 mm. In 10/31 studies, MAM quantification was performed in 3D rather than in three orthogonal image planes. Segmentations were performed either semi-automatically or manually. Rigid and non-rigid co-registration algorithms were used about as often. Tissue shrinkage rates ranged from 7% to 74%. Conclusions: There is a high variability in ablation margin quantification methods. Prospectively obtained data and a validated robust workflow are needed to better understand the clinical value. Interpretation of quantified ablation margins may be influenced by tissue shrinkage, as this may cause underestimation.

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PURPOSE: To assess short-term tissue shrinkage in patients with liver malignancies undergoing computed tomography (CT)-guided microwave ablation (MWA) using Jacobian determinant (JD). MATERIALS AND METHODS: Twenty-nine patients with 29 hepatic malignancies (primary n = 24; metastases n = 5; median tumor diameter 18 mm) referred to CT-guided MWA (single position; 10 min, 100 W) were included in this retrospective IRB-approved study, after exclusion of five patients. Following segmentation of livers and tumors on pre-interventional images, segmentations were registered on post-interventional images. JD mapping was applied to quantify voxelwise tissue volume changes after MWA. Percentual volume changes were evaluated in the ablated tumor, a 5-cm tumor perimeter and in the whole liver and compared in different clinical conditions (tumor entity: primary vs. secondary; tumor location: subcapsular vs. non-subcapsular; tumor volume: >/<6 ml: cirrhosis: yes vs. no; prior chemotherapy: yes vs. no using Shapiro-Wilk, χ2 and Wilcoxon rank sum tests, respectively (with p < 0.05 deemed significant). RESULTS: Tissue volume change was 0.6% in the ablated tumor, 1.6% in the 5-cm perimeter and 0.3% in the whole liver. Shrinkage in the ablated tumor was pronounced in non-subcapsular located tumors, whereas tissue expansion was noted in subcapsular tumors (median -3.5 vs. 1.1%; p = 0.0195). Shrinkage in the whole liver was higher in tumor volumes >6ml, compared with smaller tumors, in which tissue expansion was noted (median -1.0 vs. 2.5%; p = 0.002). Other clinical conditions had no significant influence on the extent of tissue shrinkage (p > 0.05). CONCLUSION: 3D Jacobian analysis shows that hepatic tissue deformation following MWA is most pronounced in a 5-cm area surrounding the treated tumor. Tumor location and tumor volume may have an impact on the extent of tissue shrinkage which may affect estimation of the safety margin.

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Background: The purpose of this study is to evaluate the survival rate of the basal cortical screw (BCS) implant system inserted in healed edentulous ridges (E) or extraction sockets (ES) with immediate loading functional protocol in varying clinical situations. Methods: A total of 125 BCS implants were placed in 14 patients, immediately loaded and observed for 20.07(± 4.23) months. Ninety-four were placed in E sites and 31 were placed in ES sites. They were evaluated for bone loss, soft tissue shrinkage around the prosthesis, improvement in quality of life (QOL), and their survival after 1 year. Results: Total of 121/125(96.8%) implants survived while 4/125(3.2%) failed at the end of follow-up. Average bone loss after 1 year was 0.33 mm (E) and - 1.57 mm (ES), average soft tissue shrinkage was 0.50 mm (E) and 1.42 mm (ES) and average Patient's Global Impression of Change (PGIC) scale score was 6.36(± 0.63) at 1 year. The complications observed were mobility {3(2.4%)}, pain/discomfort {1(0.8%)} and fracture of abutment at the neck {1(0.8%)}, prosthesis loosening {2(9%)} and requirement of relining {3(13%)}. No periimplantitis was observed. Conclusion: This is the only study to report the marginal bone loss and soft tissue changes around BCS implants and an index-based improvement in QOL of such patients. The BCS implant system with immediate functional loading protocol is a versatile modality to rehabilitate a single tooth, a segment or a full arch with healed ridges as well as extraction sites; it gives high success rate and minimal complications.

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Objective: To determine the shrinkage effect of formalin on renal cell carcinoma. METHODS: The retrospective study was conducted from October to November 2020 at Tekirdag Namik Kemal University, Turkey, and comprised all radical and partial nephrectomy cases performed by a single surgeon in a single clinic between January 2014 and August 2020. Pre-operative images and post-operative pathology were reviewed by the same clinician. Pre-operative longest tumour diameter of radiological images and pathological specimens measured after formalin fixation shrinkage were compared, and the effect of the difference between the two measurements on the circumference of the tumour was examined. The formalin-related shrinkage rates of renal tumours according to the tumour size and the tumour types were also analysed. Data was analysed using SPSS 20. RESULTS: Of the 101 cases, 58(57.4%) were of radical and 43(42.6%) of partial nephrectomy. Also, there were 77(76.2%) renal cell carcinoma cases, 22(21.8%) benign renal tumours and 2(1.9%) had other malignant tumours. There were 59(58.4%) males and 42(41.6%) females with an overall mean age of 58.1±12,2 years (range: 30-82 years). The mean radiological size of the renal tumours was 55.3±30.4 mm and it was 52.9±31.6 mm at pathological examination (p>0.05). Conclusion: Formalin fixation of tissues post-surgery caused a difference between the radiological and pathological dimensions. Though the difference was no significant, under-staging due to the shrinkage post-surgery should be considered.

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In this study we compare temporal lobe (TL) signal intensity (SI) profiles, along with the average thicknesses of the transient zones obtained from postmortem MRI (pMRI) scans and corresponding histological slices, to the frontal lobe (FL) SI and zone thicknesses, in normal fetal brains. The purpose was to assess the synchronization of the corticogenetic processes in different brain lobes. Nine postmortem human fetal brains without cerebral pathologies, from 19 to 24 weeks of gestation (GW) were analyzed on T2-weighted 3T pMRI, at the coronal level of the thalamus and basal ganglia. The SI profiles of the transient zones in the TL correlate well spatially and temporally to the signal intensity profile of the FL. During the examined period, in the TL, the intermediate and subventricular zone are about the size of the subplate zone (SP), while the superficial SP demonstrates the highest signal intensity. The correlation of the SI profiles and the distributions of the transient zones in the two brain lobes, indicates a time-aligned histogenesis during this narrow time window. The 3TpMRI enables an assessment of the regularity of lamination patterns in the fetal telencephalic wall, upon comparative evaluation of sizes of the transient developmental zones and the SI profiles of different cortical regions. A knowledge of normal vs. abnormal transient lamination patterns and the SI profiles is a prerequisite for further advancement of the MR diagnostic tools needed for early detection of developmental brain pathologies prenatally, especially mild white matter injuries such as lesions of TL due to prenatal cytomegalovirus infections, or cortical malformations.

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Epithelia grow and shape into functional structures during organogenesis. Although most of the focus on organogenesis has been drawn to the building of biological structures, the disassembly of pre-existing structures is also an important event to reach a functional adult organ. Examples of disassembly processes include the regression of the Müllerian or Wolffian ducts during gonad development and mammary gland involution during the post-lactational period in adult females. To date, it is unclear how organ disassembly is controlled at the cellular level. Here, we follow the Drosophila larval trachea through metamorphosis and show that its disassembly is a hormone-driven and precisely orchestrated process. It occurs in two phases: first, remodeling of the apical extracellular matrix (aECM), mediated by matrix metalloproteases and independent of the actomyosin cytoskeleton, results in a progressive shortening of the entire trachea and a nuclear-to-cytoplasmic relocalization of the Hippo effector Yorkie (Yki). Second, a decreased transcription of the Yki target, Diap1, in the posterior metameres and the activation of caspases result in the apoptotic loss of the posterior half of the trachea while the anterior half escapes cell death. Thus, our work unravels a mechanism by which hormone-driven ECM remodeling controls sequential tissue shortening and apoptotic cell removal through the transcriptional activity of Yki, leading to organ disassembly during animal development.

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BACKGROUND: In the neurosciences, the physical disector method represents an established quantitative stereological method for unbiased sampling and counting of cells in histological tissue sections of known thickness. Physical disector analyses are conventionally performed using plastic-embedded tissue samples, because plastic-embedding causes a comparably low and definable shrinkage of the embedded tissue, and the thickness of thin plastic sections can be determined adequately. However, immunohistochemistry protocols often don't work satisfactorily in sections of plastic-embedded tissue. NEW METHOD: Here, a new methodological approach is presented, allowing for physical disector analyses of immunohistochemically labeled cells in paraffin sections. The embedding-related tissue shrinkage is standardized by using defined tissue sample volumes and paraffin volumes, and the extent of tissue shrinkage can be determined accurately from the sample volumes prior to and after embedding. Co-embedding of polyethylene section thickness standards together with the tissue samples allows the precise determination of individual paraffin section thicknesses by spectral reflectance measurements. RESULTS AND COMPARISON WITH EXISTING METHOD(S): The applicability of the new method is demonstrated by physical disector analysis of immunohistochemically identified somatotroph cells in paraffin sections of porcine pituitary gland tissue. With consideration of individual shrinkage factors and section thicknesses, the cell numbers and mean volumes estimated in paraffin disector sections do not significantly differ from the results obtained by analyses of plastic-embedded pituitary tissue samples of the identical animals (2.4% average difference). CONCLUSIONS: The featured method enables combination of paraffin section immunohistochemistry and physical disector analyses for unbiased quantitative stereological analyses of different cell types.

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The purpose of the study was to investigate the interrelation of the signal intensities and thicknesses of the transient developmental zones in the cingulate and neocortical telencephalic wall, using T2-weighted 3 T-magnetic resonance imaging (MRI) and histological scans from the same brain hemisphere. The study encompassed 24 postmortem fetal brains (15-35 postconceptional weeks, PCW). The measurements were performed using Fiji and NDP.view2. We found that T2w MR signal-intensity curves show a specific regional and developmental stage profile already at 15 PCW. The MRI-histological correlation reveals that the subventricular-intermediate zone (SVZ-IZ) contributes the most to the regional differences in the MRI-profile and zone thicknesses, growing by a factor of 2.01 in the cingulate, and 1.78 in the neocortical wall. The interrelations of zone or wall thicknesses, obtained by both methods, disclose a different rate and extent of shrinkage per region (highest in neocortical subplate and SVZ-IZ) and stage (highest in the early second half of fetal development), distorting the zones' proportion in histological sections. This intrasubject, slice-matched, 3 T correlative MRI-histological study provides important information about regional development of the cortical wall, critical for the design of MRI criteria for prenatal brain monitoring and early detection of cortical or other brain pathologies in human fetuses.

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BACKGROUND: Microwave ablation (MWA) is a minimally invasive treatment option for solid tumors and belongs to the local ablative therapeutic techniques, based on thermal tissue coagulation. So far there are mainly ex vivo studies that describe tissue shrinkage during MWA. PURPOSE: To characterize short-term volume changes of the ablated zone following hepatic MWA in an in vivo porcine liver model using contrast-enhanced computer tomography (CECT). MATERIAL AND METHODS: We performed multiple hepatic MWA with constant energy parameters in healthy, narcotized and laparotomized domestic pigs. The volumes of the ablated areas were calculated from venous phase CT scans, immediately after the ablation and in short-term courses of up to 2 h after MWA. RESULTS: In total, 19 thermally ablated areas in 10 porcine livers could be analyzed (n = 6 with two volume measurements during the measurement period and n = 13 with three measurements). Both groups showed a statistically significant but heterogeneous volume reduction of up to 12% (median 6%) of the ablated zones in CECT scans during the measurement period (P < 0.001 [n = 13] and P = 0.042 [n = 6]). However, the dimension and dynamics of volume changes were heterogenous both absolutely and relatively. CONCLUSION: We observed a significant short-term volume reduction of ablated liver tissue in vivo. This volume shrinkage must be considered in clinical practice for technically successful tumor treatment by MWA and therefore it should be further investigated in in vivo studies.

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The morphological structure of neurons provides the basis for their functions and is a major focus of contemporary neuroscience studies. Intracellular staining of single cells in acute slices is a well-established approach, offering high-resolution information on neuronal morphology, complementing their physiology. Despite major technical advances, however, a common histological artifact often precludes precise morphological analysis: shrinkage of the sampled tissue after embedding for microscopy. Here, we describe a new approach using a metal spacer, sandwiched between two coverslips to reduce shrinkage of whole-mount slice preparations during embedding with aqueous mounting medium under a coverslip. This approach additionally allows imaging the slices from both sides to obtain better quality images of deeper structures. We demonstrate that the use of this spacer system can efficiently and stably reduce the shrinkage of slices, whereas conventional embedding methods without spacer or with agar spacer cause severe, progressive shrinkage after embedding. We further show that the shrinkage of slices is not uniform and artifacts in morphology and anatomical parameters produced cannot be compensated using linear correction algorithms. Our study, thus, emphasizes the importance of preventing the deformation of slice preparations and offers an effective means for reducing shrinkage and associated artifacts during embedding.

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The optical disector, a three-dimensional counting frame or probe in stereology, is often positioned in the middle (depth) of a thick section for unbiased nuclear counting. Using 30-40 µm thick methacrylate or paraffin sections for nuclear counting of neurons with the optical disector, however, some studies showed markedly higher nuclear densities at 10% of the section thickness near the top or bottom surface of the section, suggestive of deformation of section along its z axis and thus affecting the number estimation. To verify the findings, this study obtained two sets of 12-14 methacrylate sections (average thicknesses 21.7 and 29.4 µm) and two sets of 12 paraffin sections (average thicknesses 13.8 and 29.2 µm) from mature rat testes. Each section was used to count round spermatid nuclei in the seminiferous epithelium densely packed with the cells, using 3-4 consecutive disectors placed vertically (along the z axis of the section) from the top surface of the section, through the whole section thickness (two sets of methacrylate and paraffin sections) or in 80-83% of the thickness (other sections). The results demonstrated that, overall, there were no considerable nonuniform changes of the nuclear densities along the z axis of the sections.

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Cell death, a process which can occur both naturally and in response to insult, is both a complex and diverse phenomenon. Under some circumstances, dying cells actively contract and cause their neighbors to rearrange and maintain tissue integrity. Under other circumstances, dying cells leave behind gaps, which results in tissue separation. A better understanding of how the cellular scale features of cell death manifest on the population scale has implications ranging from morphogenesis to tumor response to treatment. However, the mechanistic relationship between cell death and population scale shrinkage is not well understood, and computational methods for studying these relationships are not well established. Here we propose a mechanically robust agent-based cell model designed to capture the implications of cell death on the population scale. In our agent-based model, algorithmic rules applied on the cellular level emerge on the population scale where their effects are quantified. To better quantify model uncertainty and parameter interactions, we implement a recently developed technique for conducting a variance-based sensitivity analysis on the stochastic model. From this analysis and subsequent investigation, we find that cellular scale shrinkage has the largest influence of all model parameters tested, and that by adjusting cellular scale shrinkage population shrinkage varies widely even across simulations which contain the same fraction of dying cells. We anticipate that the methods and results presented here are a starting point for significant future investigation toward quantifying the implications of different mechanisms of cell death on population and tissue scale behavior.

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Quantitative data on lung structure, such as volume, surface area and length, are used for assessment of the functional performance of the lung during normal development and inflammatory-related diseases such as chronic obstructive pulmonary disorder (COPD), and carcinogenesis, in animal models. Stereology is considered as the gold standard to obtain quantitative data on lung structure, with a key advantage being to quantify irregular three-dimensional structures on the basis of measurement made on two-dimensional sections. Therefore, preservation of original tissue dimensions without shrinkage is vital for stereology.Three steps, fixation, sampling and embedding, are essential requirements to minimise tissue shrinkage to obtain theoretically unbiased estimates of stereological parameters of lung structures. Perfusion fixation by intratracheal instillation with 1.5% glutaraldehyde/1.5% formaldehyde at a pressure of 25 cm fluid column is considered as one of the best methods. A systematic uniform random sampling scheme is then applied to the fixed lung to ensure each and every part of the lung is analysed, irrespective of homogeneity or heterogeneity of the structural distribution. The sampled tissue sections are then embedded in glycol methacrylate to minimise further tissue shrinkage. Here we describe the accurate fixation, sampling and embedding for stereological methods to quantify lung structures in mice.

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PURPOSE: To evaluate, characterise and compare the extent of tissue shrinkage induced from three different commercial microwave ablation devices, and to elucidate the mechanism behind the distinctive performances obtained. MATERIALS AND METHODS: Microwave ablation (N = 152) was conducted with three different commercial devices on cubes of ex vivo liver (10-40 ± 2 mm/side) embedded in agar phantoms. 50-60 W was applied for 1-10 min duration. Pre- and post-ablation dimensions of the samples, as well as the extent of carbonisation and coagulation were measured and correlated. ANOVA was performed to evaluate statistical significance. RESULTS: For all devices, logarithmic correlations with time were observed for both tissue shrinkage (R2 = 0.84-1.00) and induced carbonisation (R2 = 0.73-0.99) radially to the antenna axis. Along the longitudinal axis of the antenna, for two of the devices shrinkage did not appreciably change with time (p > 0.05), yet carbonisation increased linearly (R2 = 0.57-0.94). For the third fully internally-cooled device, both carbonisation and shrinkage showed logarithmic trends (R2 = 0.85-0.98 and R2 = 0.78-0.94, respectively) based upon delayed carbonisation appearing only 5 min into ablation and onward. For all devices, non-uniform shrinkage was noted within the coagulated area increasing from the boundary of the ablated area (14%) to the limit of carbonisation (39%) in a linear fashion (R2 = 0.88) Conclusions: Microwave ablation device construction can alter the extent of post-ablation coagulation and tissue shrinkage. Given that tissue shrinkage in the coagulated area shows non-uniform behaviour, observed differences can be attributed in part to the applicator cooling system that alters the ablation temperature profile.

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Mummification leads to alteration of soft-tissue morphology. No research has focused specifically on differences in soft-tissue shrinkage depending on mummification type. This study evaluated whether soft-tissue alteration is dependent on type of mummification. A total of 17 human mummies have been investigated by computed tomography (CT). Samples included artificially embalmed ancient Egyptian mummies, naturally mummified South American corpses, ice mummies (including the Iceman, South Tyrol Museum of Archeology, Bolzano, Italy, ca. 3,300 BC), bog bodies and a desiccated mummy of possibly Asian provenance. The acquired data were compared to four contemporary bodies. The extent of soft-tissue shrinkage was evaluated using CT data. Shrinkage was defined as soft-tissue relative to area of bone (in number of voxels). Measurements were taken at 13 anatomically defined locations. Ice mummies show the highest degree of preservation. This finding is most likely explained due to frozen water within tissues. All other types of mummies show significantly (at P < 0.05) smaller relative area of preserved soft-tissue. Variation between different anatomical structures (e.g., upper lip vs. mid-femur) is significant, unlike variation within one compartment (e.g., proximal vs. distal humerus). Mummification type strongly affects the degree of soft-tissue alteration, surprisingly mostly independent of overall historical age. These results highlight the unique morphological impact of taphonomy on soft-tissue preservation and are of particular interest in tissue research as well as in forensics.

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PURPOSE: The aim of this study was to characterise changes in tissue volume during image-guided microwave ablation in order to arrive at a more precise determination of the true ablation zone. MATERIALS AND METHODS: The effect of power (20-80 W) and time (1-10 min) on microwave-induced tissue contraction was experimentally evaluated in various-sized cubes of ex vivo liver (10-40 mm ± 2 mm) and muscle (20 and 40 mm ± 2 mm) embedded in agar phantoms (N = 119). Post-ablation linear and volumetric dimensions of the tissue cubes were measured and compared with pre-ablation dimensions. Subsequently, the process of tissue contraction was investigated dynamically during the ablation procedure through real-time X-ray CT scanning. RESULTS: Overall, substantial shrinkage of 52-74% of initial tissue volume was noted. The shrinkage was non-uniform over time and space, with observed asymmetry favouring the radial (23-43 % range) over the longitudinal (21-29%) direction. Algorithmic relationships for the shrinkage as a function of time were demonstrated. Furthermore, the smallest cubes showed more substantial and faster contraction (28-40% after 1 min), with more considerable volumetric shrinkage (>10%) in muscle than in liver tissue. Additionally, CT imaging demonstrated initial expansion of the tissue volume, lasting in some cases up to 3 min during the microwave ablation procedure, prior to the contraction phenomenon. CONCLUSIONS: In addition to an asymmetric substantial shrinkage of the ablated tissue volume, an initial expansion phenomenon occurs during MW ablation. Thus, complex modifications of the tissue close to a radiating antenna will likely need to be taken into account for future methods of real-time ablation monitoring.

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Mass spectrometry (MS) was used to measure the concentrations of drug and biological compounds in plasma and tissues. Matrix-assisted laser desorption/ionization (MALDI) imaging MS (IMS) has recently been applied to the analysis of localized drugs on biological tissue surfaces. In MALDI-IMS, matrix application process is crucial for successful results. However, it is difficult to obtain homogeneous matrix crystals on the tissue surface due to endogenous salts and tissue surface heterogeneity. Consequently, the non-uniform crystals degrade the quality of the spectrum and likely cause surface imaging artifacts. Furthermore, the direct application of matrix solution can cause tissue shrinkage due to the organic solvents. Here, we report an alternative two-step matrix application protocol which combines the vacuum deposition of matrix crystals and the spraying of matrix solution to produce a homogeneous matrix layer on the tissue surface. Our proposed technique can also prevent cracking or shrinking of the tissue samples and improve the ionization efficiency of the distributed exogenous material.

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