Breast Surgery : Margin Assessment and Complications

Rintasyövän leikkaushoidossa pyritään poistamaan kasvain kokonaisuudessaan riittävällä tervekudosmarginaalilla. Riittämätön leikkausmarginaali lisää paikallisuusiutuman riskiä ja heikentää potilaan ennustetta. Tämän takia potilaalle tehdään usein uusintaleikkaus, jos tervekudosmarginaali on riittämätön. Leikkauksen jälkeen patologi dissekoi leikkauspreparaatin ja ottaa kasvaimesta sekä marginaalista edustavat näytteet, minkä jälkeen tervekudosmarginaali määritetään mikroskooppisesti. Leikkauspreparaatin dissektio ja edustava näytteenotto voi kuitenkin olla haastavaa. Lisäksi riittävää tervekudosmarginaalia käsittelevät hoitosuositukset ovat ristiriitaisia koskien intraduktaalista karsinoomaa (DCIS), joka on todettu samanaikaisesti invasiivisen karsinooman kanssa. Joka viides potilas leikataan uudestaan rinnan säästävän leikkauksen jälkeen. Positiivinen leikkausmarginaali ei kuitenkaan aina johda uusintaleikkaukseen, ja uusintaleikkauskäytännöt ovat vaihtelevia. Tässä väitöskirjassa tutkitaan kattava otos patologisia lausuntoja ja selvitetään tekijöitä, jotka ohjaavat uusintaleikkauspäätöstä (osajulkaisu III). Rintojen pienennysleikkauksella hoidetaan rintojen liikakasvua yksilöllisen arvion perusteella. Leikkauskomplikaatiot rintojen pienennysleikkausten jälkeen ovat samankaltaisia kuin rintasyövän leikkaushoidon jälkeen. Rintojen pienennysleikkauksen jälkeisten postoperatiivisten leikkauskomplikaatioiden tutkiminen edesauttaa riskipotilaiden tunnistamista myös onkologisessa rintakirurgiassa. Osajulkaisussa I tutkitaan rintojen pienennysleikkausten postoperatiivisia komplikaatioita sekä niille altistavia riskitekijöitä. Rintasyövän intraoperatiiviseen tunnistamiseen soveltuva menetelmä voisi vähentää riittämättömän tervekudosmarginaalin takia tehtyjen uusintaleikkausten määrää. Vastaavaa kudoskuvantamiseen soveltuvaa menetelmää voisi hyödyntää rinnan leikkauspreparaatin dissektiossa ja näytteenotossa. Erilaisia kudostunnistusmenetelmiä on tutkittu viime vuosina runsaasti, mutta yksikään näistä ei ole vakiinnuttanut asemaansa kliinisessä käytössä. Differentiaali mobiliteetti spektrometrialla (DMS) voidaan analysoida nopeasti ja kustannustehokkaasti kaasuseoksia. Esittelemme kaksi DMS-analyysiin perustuvaa menetelmää: 1) intraoperatiiviseen marginaalin tunnistamiseen (osajulkaisu II) ja 2) kudoskuvantamiseen (osajulkaisu IV). Osajulkaisussa I analysoimme tiedot potilaista, joille tehtiin rintojen pienennysleikkaus Tampereen yliopistollisessa sairaalassa (Tays) vuosina 2000−2010 (n = 453). Polikliinisesti hoidetut komplikaatiot luokiteltiin lieviksi. Komplikaatiot luokiteltiin vakaviksi, jos potilas otettiin osastohoitoon tai leikattiin uudelleen. Osajulkaisussa III analysoimme patologin lausunnoista kerätyt tiedot rintasyöpäpotilaista, jotka leikattiin Turun yliopistollisessa sairaalassa (Tyks) vuosina 2000−2018 (n = 4489). Invasiivisen karsinooman osalta marginaalipositiivisuus määriteltiin musteena karsinoomasolukon pinnalla mikroskopiassa. Intraduktaalisessa karsinoomassa sovellettiin 2 mm:n etäisyyttä anterioriseen marginaaliin ja sivumarginaaliin; posteriorisessa marginaalissa marginaalipositiivisuus määriteltiin musteena karsinoomasolukon pinnalla. Analysoimme eläinkudoksia laserpohjaisella DMS-järjestelmällä osajulkaisussa IV. Selvitimme DMS:n soveltuvuutta 1) kudosmatriisien sisäiseen luokitteluun ja 2) itsenäisen kudosmatriisin luokitteluun. Tämän jälkeen tutkimme rintasyövän tunnistamista DMS:lla osajulkaisuissa II ja IV. Karsinoomanäytteet kerättiin palpoituvista tuumoreista, jotka olivat suurimmalta läpimitaltaan vähintään 21 mm (≥ cT2). Osajulkaisussa II analysoimme DMS:lla malignia ja benigniä rintakudosta edustavia stanssibiopsioita, jotka kerättiin 21 potilaalta. Näytteet analysoitiin Automaattisella kudostunnistusjärjestelmällä (ATAS), joka tuottaa palokaasua sähköveitsen avulla. Osajulkaisussa IV analysoimme kolmen rintasyöpänäytteen poikkileikkeet Automaattisella laserpohjaisella kudoskuvantamisjärjestelmällä (iATLAS). Rintojen pienennysleikkauksen jälkeen potilaista 41 %:lla todettiin lievä komplikaatio ja 9 %:lla vakava komplikaatio. Lievän leikkauskomplikaation saaneiden potilaiden keskimääräinen BMI oli huomattavasti korkeampi (30 kg/m2) kuin potilailla, joilla ei todettu komplikaatioita (28 kg/m2; p < 0.001). Potilailla, joiden BMI ylitti 27 kg/m2 oli 2,6-kertainen riski saada lievä komplikaatio (p < 0.001). BMI:n nousu yhdellä yksiköllä lisäsi lievien komplikaatioiden riskiä 14 % (p< 0.001). Rintasyövän säästävän leikkauksen jälkeen 20 %:lla ja mastektomian jälkeen 5 %:lla potilaista todettiin positiivinen sivumarginaali (p < 0.001). Näistä potilaista 68 % ja 14 % leikattiin uudelleen. Alle 80-vuotiaista potilaista 68–74 % uusintaleikattiin positiivisen sivumarginaalin jälkeen, kun taas tämän iän ylittäneistä vain 42 % leikattiin uudestaan (p = 0.013). Kun DCIS sijaitsi sivumarginaalin lähellä (≤ 1,0 mm), 70 % potilaista leikattiin uudelleen. Sen sijaan tätä kauempana sijaitseva DCIS (1,1–2,0 mm) johti uusintaleikkaukseen vain 43 %:lla potilaista (p = 0.002). Sivumarginaalin lähellä sijaitseva DCIS osana invasiivista karsinoomaa johti uusintaleikkaukseen 55 %:lla, ekstensiivinen intraduktaalinen komponentti (EIC) 66 %:lla ja puhdas DCIS 83 %:lla (p < 0.001). Saavutimme DMS:lla 86 % luokittelutarkkuuden sian luustolihakselle (n = 1030), rasvakudokselle (n = 1329), tavalliselle rintakudokselle (n=258), luulle (n = 680) ja maksalle (n = 264). Itsenäisen kudosmatriisin luokittelussa saavutimme 82 % luokittelutarkkuuden. Rintasyövän (n = 106) ja hyvänlaatuisen rintakudoksen (n = 198) luokittelutarkkuus ATASilla oli 87 %, sensitiivisyys 80 % ja spesifisyys 90 %. Kolmen rintasyöpäleikkeen makroskooppisesti annotoiduilla mittauksilla saavutettiin iATLAS-järjestelmällä 94 % luokittelutarkkuus, 95 % spesifisyys ja 93 % sensitiivisyys. Leikkeistä kaksi soveltui mikroskooppiseen annotaatioon. Ensimmäisen leikkeen luokittelutarkkuus oli 84 %, spesifisyys 88 % ja sensitiivisyys 77 %. Toisen leikkeen osalta vastaavat arvot olivat 72 %, 88 % ja 24 %. Korkea BMI oli yhteydessä lieviin leikkauskomplikaatioihin rintojen pienennysleikkauksen jälkeen. Ylipainoisille potilaille tulee kertoa tästä riskistä ja kannustaa heitä painonpudotukseen. Uusintaleikkauspäätös perustui yksilölliseen harkintaan positiivisen sivumarginaalin jälkeen rintasyöpäleikkauksessa. Leikkaustapa, potilaan ikä sekä DCIS:n tyyppi ja etäisyys sivumarginaalista ohjasivat uusintaleikkauspäätöstä. DMS-analyysi soveltuu kudostunnistukseen ja voi jatkossa soveltua intraoperatiivisen leikkausmarginaalin analyysiin sekä kudoskuvantamiseen ennen mikroskopiaa.The surgical oncology of breast cancer aims to remove the entire tumor with sufficient surgical margins. Inadequate margins increase the risk of a local recurrence and impair the overall survival of patients. Thus, inadequate margins often necessitate a reoperation. The margin status is determined postoperatively by a pathologist during the gross and microscopic examination of the surgical specimen. However, gross examination is not always straightforward, and the optimal margin width for ductal carcinoma in situ (DCIS) diagnosed alongside invasive carcinoma remains controversial.Currently, approximately one in five patients undergo a reoperation after breast- conserving surgery (BCS), but the reoperation rates do not equal positive margin rates and there is considerable variation in reoperation practices. In this doctoral thesis, we provide a detailed assessment of histopathology reports to better understand the factors that lead to a reoperation (study III). Reduction mammoplasty is an elective operation, whereas breast cancer surgery is performed on a vital indication. However, the postoperative complication profiles of reduction mammoplasty, BCS, and mastectomy reflect one another. The examination of postoperative complications after reduction mammoplasty also provides data on the recognition of high-risk patients in surgical oncology. Herein, we investigate a series of reduction mammoplasties to assess the risk factors for complications after reduction mammoplasty (study I). A tool for intraoperative breast cancer identification could reduce reoperations due to margin positivity. Similarly, tissue imaging before a pathological gross examination could enable focused sampling of breast specimens without compromising diagnostic accuracy. In recent years, such methods have been extensively studied, but none have been adopted into routine practice. Differential mobility spectrometry (DMS) enables the analysis of complex gas mixtures. DMS can offer a robust and cost-efficient means of breast cancer identification from evaporated tissues. We present two DMS-based systems for 1) intraoperative margin assessment (study II) and 2) tissue imaging (study IV). In study I, we analyzed the clinical data of patients who underwent reduction mammoplasty at Tampere University Hospital (Tays) between 2007 and 2010 (n =453). Complications treated on an outpatient basis were classified as minor and those demanding readmission or a reoperation as major. In study III, we analyzed the histopathological data of breast cancer patients (n = 4,489) operated on at Turku University Hospital (Tyks) between 2000 and 2018. Margin positivity was defined as ink on tumor for invasive carcinoma. For DCIS, we applied 2 mm anterior and side margin thresholds and ink on tumor in the posterior margin. We analyzed a series of porcine tissues with laser-based DMS in study IV. We examined DMS in 1) matrix-wise tissue identification and 2) the classification of an independent validation set. Next, we studied breast cancer identification with DMS in studies II and IV. The carcinoma samples were of 1) a palpable tumor and 2) tumor size exceeding 21 mm (≥ cT2). In study II, we collected malignant and benign punch biopsies (4 mm) from twenty-one breast cancer patients. The samples were analyzed with the Automated Tissue Analysis System (ATAS), which utilized a diathermy blade for tissue evaporation. In study IV, we analyzed cross-sections of three breast carcinomas with the Automated Tissue Laser Analysis System for imaging approaches (iATLAS). After reduction mammoplasty, the incidence of minor and major complications was 41% and 9%, respectively. Patients with minor complications had a significantly higher mean BMI (30 kg/m2) than patients who recovered without complications (28 kg/m2; p < 0.001). Patients with a BMI higher than 27 kg/m2 had a 2,6-fold greater risk of minor complications (p < 0.001). An increase of one unit in BMI increased the probability of minor complications by 14% (p < 0.001). After breast cancer, the incidence of positive side margins was higher in BCS (20%) compared to mastectomy (5%; p < 0.001). Of these patients, a respective 68% and 14% were reoperated on (p < 0.001). Young patients underwent a reoperation significantly more often (68%−74%) than those aged more than 80 years (42%; p = 0.013). DCIS located close (≤ 1 mm) to the side margin led to a reoperation in 70% of the cases, whereas those with a wider (1.1–2 mm) margin underwent a reoperation in 43% of the cases (p = 0.002). The reoperation rates were 55% for invasive carcinoma with a close DCIS margin, 66% for a close intraductal component (EIC) margin, and 83% for close pure DCIS margin (p < 0.001). We achieved a classification accuracy of 86% for porcine skeletal muscle (n = 1,030), adipose tissue (n = 1,329), normal breast tissue (n = 258), bone (n = 680), and liver (n = 264) with DMS data. In the independent validation set analysis, we achieved a classification accuracy of 82% with the previously constructed classification model. With ATAS, the classification accuracy of breast cancer (n = 106) and benign breast tissue (n = 198) was 87%, with a sensitivity of 80% and specificity of 90%. With iATLAS, we reached a classification accuracy of 94%, specificity of 94%, and sensitivity of 93% for the macroscopically annotated data from three breast cancer specimens. The microscopic annotation was applicable to two specimens. For the first specimen, the classification accuracy was 84%, specificity 88%, and sensitivity 77%. For the second specimen, the classification accuracy was 72%, specificity 88%, and sensitivity 24%. A higher BMI was strongly associated with an increased risk of minor complications after reduction mammoplasty. It is important to inform obese patients about the increased risk and to encourage them to lose weight before surgery. Individual assessment as opposed to rigid adherence to guidelines was applied in the decision on whether to reoperate after side margin positivity in surgical oncology. Operation type, DCIS type and the component’s distance from the side margin, as well as the patient’s age guided the decision on whether to reoperate. DMS analysis of evaporated tissues is suitable for tissue identification. In the future, DMS analysis could be efficient in intraoperative margin assessment and tissue imaging before traditional microscopy

Supporting the peace mediation efforts of religious leaders : an empirical study of co-operation between Finnish NGOs and the Ministry for Foreign Affairs of Finland

The complex, protracted nature of contemporary conflicts poses increasingly significant challenges to the resolution of armed conflicts. Traditional peace mediation has proven largely inefficient in responding to the modern security challenges presented by conflicts revolving around religious and ethno-political affiliations or other issues related to perceptions of group identity. As new strategies of addressing these modern security threats have become necessary, the field of mediation has witnessed a growing emphasis on localised mediation and local ownership of peace processes, often spearheaded by non-official diplomacy. The conventional ideal of neutral, outsider third parties is more and more often replaced by new types of insider mediators. These include local religious leaders, whose mediation capacity is seen as rooted in the trust and credibility they enjoy in their communities. The increasing global attention on the peace efforts of religious leaders has also been highly visible in Finland, which has begun to promote the work of religious peacemakers as part of its mediation policy. In light of this shift, the thesis set out to study how Finnish diplomats and non-official practitioners view the role of religious leaders, how the NGOs support the peace efforts of religious leaders and how the Ministry for Foreign Affairs of Finland (MFA) supports this work. In order to do this, the study conducted an empirical study of the work of three Finland-based non-official organisations (NGOs) active in the field: Finn Church Aid, the Network for Religious and Traditional Peacemakers and the Finnish Evangelical Lutheran Mission. It also studied their co-operation with the Ministry for Foreign Affairs of Finland and the effect of this collaboration on each party. This was done through the qualitative analysis of semi-structured interviews and written project documents, which were examined through the framework of conflict transformation, focusing specifically on John Paul Lederach s peacebuilding pyramid and Andrea Strimling s model of co-operation between official and non-official diplomats. The study found that despite certain differences of opinion regarding the type of religious leaders that can most effectively advance peace, the mediation experts from both the MFA and the NGOs have a similar view of the strengths and the general role of religious leaders in peacemaking. It argued that the NGOs play a central role in connecting local religious leaders to other actors, including states and international organisations. It also concluded that the NGOs' work has benefited from their co-operation with the MFA, which has similarly profited from its co-operation with the NGOs. The thesis found that, in addition to the growing acknowledgement of the importance of multi-track co-operation in the field in general, this partnership has been enabled by certain context-specific factors, such as the parties' similar or non-conflicting interests and goals, an existing structure of co-operation between the state and civil society, professional cultures that do not pose significant challenges to co-operation, mutual recognition of the power-related benefits of co-operation and strong working relationships between individuals

Tumor margins that lead to reoperation in breast cancer: A retrospective register study of 4,489 patients

Background and Objectives Optimal margins for ductal carcinoma in situ (DCIS) remain controversial in breast-conserving surgery (BCS) and mastectomy. We examine the association of positive margins, reoperations, DCIS and age. Methods A retrospective study of histopathological reports (4489 patients). Margin positivity was defined as ink on tumor for invasive carcinoma. For DCIS, we applied 2 mm anterior and side margin thresholds, and ink on tumor in the posterior margin. Results The incidence of positive side margins was 20% in BCS and 5% in mastectomies (p p p = 0.013). Of BCS patients with invasive carcinoma in the side margin, 73% were reoperated on. A reoperation was performed in 70% of patients with a close (p = 0.002). The reoperation rates were 55% in invasive carcinoma with close DCIS, 66% in close extensive intraductal component (EIC), and 83% in close pure DCIS (p Conclusions Individual assessment as opposed to rigid adherence to guidelines was used in the decision on reoperation.</p

Detection of cultured breast cancer cells from human tumor-derived matrix by differential ion mobility spectrometry

Publisher Copyright: © 2022 The AuthorsThe primary treatment of breast cancer is the surgical removal of the tumor with an adequate healthy tissue margin. An intraoperative method for assessing surgical margins could optimize tumor resection. Differential ion mobility spectrometry (DMS) is applicable for tissue analysis and allows for the differentiation of malignant and benign tissues. However, the number of cancer cells necessary for detection remains unknown. We studied the detection threshold of DMS for cancer cell identification with a widely characterized breast cancer cell line (BT-474) dispersed in a human myoma-based tumor microenvironment mimicking matrix (Myogel). Predetermined, small numbers of cultured BT-474 cells were dispersed into Myogel. Pure Myogel was used as a zero sample. All samples were assessed with a DMS-based custom-built device described as “the automated tissue laser analysis system” (ATLAS). We used machine learning to determine the detection threshold for cancer cell densities by training binary classifiers to distinguish the reference level (zero sample) from single predetermined cancer cell density levels. Each classifier (sLDA, linear SVM, radial SVM, and CNN) was able to detect cell density of 3700 cells μL−1 and above. These results suggest that DMS combined with laser desorption can detect low densities of breast cancer cells, at levels clinically relevant for margin detection, from Myogel samples in vitro.Peer reviewe

Characterization of signal kinetics in real time surgical tissue classification system

Effective surgical margin assessment is paramount for good oncological outcomes and new methods are in active development. One emerging approach is the analysis of the chemical composition of surgical smoke from tissues. Surgical smoke is typically removed with a smoke evacuator to protect the operating room staff from its harmful effects to the respiratory system. Thus, analysis of the evacuated smoke without disturbing the operation is a feasible approach. Smoke transportation is subject to lags that affect system usability. We analyzed the smoke transportation delay and evaluated its effects to tissue classification with differential mobility spectrometry in a simulated setting using porcine tissues. With a typical smoke evacuator setting, the front of the surgical plume reaches the analysis system in 380 ms and the sensor within one second. For a typical surgical incision (duration 1.5 s), the measured signal reaches its maximum in 2.3 s and declines to under 10% of the maximum in 8.6 s from the start of the incision. Two-class tissue classification was tested with 2, 3, 5, and 11 s repetition rates resulting in no significant differences in classification accuracy, implicating that signal retention from previous samples is mitigated by the classification algorithm.publishedVersionPeer reviewe

Supporting the peace mediation efforts of religious leaders : an empirical study of co-operation between Finnish NGOs and the Ministry for Foreign Affairs of Finland

The complex, protracted nature of contemporary conflicts poses increasingly significant challenges to the resolution of armed conflicts. Traditional peace mediation has proven largely inefficient in responding to the modern security challenges presented by conflicts revolving around religious and ethno-political affiliations or other issues related to perceptions of group identity. As new strategies of addressing these modern security threats have become necessary, the field of mediation has witnessed a growing emphasis on localised mediation and local ownership of peace processes, often spearheaded by non-official diplomacy. The conventional ideal of neutral, outsider third parties is more and more often replaced by new types of insider mediators. These include local religious leaders, whose mediation capacity is seen as rooted in the trust and credibility they enjoy in their communities. The increasing global attention on the peace efforts of religious leaders has also been highly visible in Finland, which has begun to promote the work of religious peacemakers as part of its mediation policy. In light of this shift, the thesis set out to study how Finnish diplomats and non-official practitioners view the role of religious leaders, how the NGOs support the peace efforts of religious leaders and how the Ministry for Foreign Affairs of Finland (MFA) supports this work. In order to do this, the study conducted an empirical study of the work of three Finland-based non-official organisations (NGOs) active in the field: Finn Church Aid, the Network for Religious and Traditional Peacemakers and the Finnish Evangelical Lutheran Mission. It also studied their co-operation with the Ministry for Foreign Affairs of Finland and the effect of this collaboration on each party. This was done through the qualitative analysis of semi-structured interviews and written project documents, which were examined through the framework of conflict transformation, focusing specifically on John Paul Lederach s peacebuilding pyramid and Andrea Strimling s model of co-operation between official and non-official diplomats. The study found that despite certain differences of opinion regarding the type of religious leaders that can most effectively advance peace, the mediation experts from both the MFA and the NGOs have a similar view of the strengths and the general role of religious leaders in peacemaking. It argued that the NGOs play a central role in connecting local religious leaders to other actors, including states and international organisations. It also concluded that the NGOs' work has benefited from their co-operation with the MFA, which has similarly profited from its co-operation with the NGOs. The thesis found that, in addition to the growing acknowledgement of the importance of multi-track co-operation in the field in general, this partnership has been enabled by certain context-specific factors, such as the parties' similar or non-conflicting interests and goals, an existing structure of co-operation between the state and civil society, professional cultures that do not pose significant challenges to co-operation, mutual recognition of the power-related benefits of co-operation and strong working relationships between individuals

Tumor margins that lead to reoperation in breast cancer : A retrospective register study of 4,489 patients

Background and Objectives: Optimal margins for ductal carcinoma in situ (DCIS) remain controversial in breast-conserving surgery (BCS) and mastectomy. We examine the association of positive margins, reoperations, DCIS and age. Methods: A retrospective study of histopathological reports (4489 patients). Margin positivity was defined as ink on tumor for invasive carcinoma. For DCIS, we applied 2 mm anterior and side margin thresholds, and ink on tumor in the posterior margin. Results: The incidence of positive side margins was 20% in BCS and 5% in mastectomies (p < 0.001). Of these patients, 68% and 14% underwent a reoperation (p < 0.001). After a positive side margin in BCS, the reoperation rates according to age groups were 74% (<49), 69% (50–64), 68% (65–79), and 42% (80+) (p = 0.013). Of BCS patients with invasive carcinoma in the side margin, 73% were reoperated on. A reoperation was performed in 70% of patients with a close (≤1 mm) DCIS side margin, compared to 43% with a wider (1.1–2 mm) margin (p = 0.002). The reoperation rates were 55% in invasive carcinoma with close DCIS, 66% in close extensive intraductal component (EIC), and 83% in close pure DCIS (p < 0.001). Conclusions: Individual assessment as opposed to rigid adherence to guidelines was used in the decision on reoperation.publishedVersionPeer reviewe

Laser desorption tissue imaging with Differential Mobility Spectrometry

Pathological gross examination of breast carcinoma samples is sometimes laborious. A tissue pre-mapping method could indicate neoplastic areas to the pathologist and enable focused sampling. Differential Mobility Spectrometry (DMS) is a rapid and affordable technology for complex gas mixture analysis. We present an automated tissue laser analysis system for imaging approaches (iATLAS), which utilizes a computer-controlled laser evaporator unit coupled with a DMS gas analyzer. The system is demonstrated in the classification of porcine tissue samples and three human breast carcinomas. Tissue samples from eighteen landrace pigs were classified with the system based on a pre-designed matrix (spatial resolution 1–3 mm). The smoke samples were analyzed with DMS, and tissue classification was performed with several machine learning approaches. Porcine skeletal muscle (n = 1030), adipose tissue (n = 1329), normal breast tissue (n = 258), bone (n = 680), and liver (n = 264) were identified with 86% cross-validation (CV) accuracy with a convolutional neural network (CNN) model. Further, a panel tissue that comprised all five tissue types was applied as an independent validation dataset. In this test, 82% classification accuracy with CNN was achieved. An analogous procedure was applied to demonstrate the feasibility of iATLAS in breast cancer imaging according to 1) macroscopically and 2) microscopically annotated data with 10-fold CV and SVM (radial kernel). We reached a classification accuracy of 94%, specificity of 94%, and sensitivity of 93% with the macroscopically annotated data from three breast cancer specimens. The microscopic annotation was applicable to two specimens. For the first specimen, the classification accuracy was 84% (specificity 88% and sensitivity 77%). For the second, the classification accuracy was 72% (specificity 88% and sensitivity 24%). This study presents a promising method for automated tissue imaging in an animal model and lays foundation for breast cancer imaging.publishedVersionPeer reviewe

Differential mobility spectrometry imaging for pathological applications

Pathologic examination of clinical tissue samples is time consuming and often does not involve the comprehensive analysis of the whole specimen. Automated tissue analysis systems have potential to make the workflow of a pathologist more efficient and to support in clinical decision-making. So far, these systems have been based on application of mass spectrometry imaging (MSI). MSI provides high fidelity and the results in tissue identification are promising. However, the high cost and need for maintenance limit the adoption of MSI in the clinical setting. Thus, there is a need for new innovations in the field of pathological tissue imaging. In this study, we show that differential ion mobility spectrometry (DMS) is a viable option in tissue imaging. We demonstrate that a DMS-driven solution performs with up to 92% accuracy in differentiating between two grossly distinct animal tissues. In addition, our model is able to classify the correct tissue with 81% accuracy in an eight-class setting. The DMS-based system is a significant innovation in a field dominated by mass-spectrometry-based solutions. By developing the presented platform further, DMS technology could be a cost-effective and helpful tool for automated pathological analysis.acceptedVersionPeer reviewe