Histological Validation Research Articles

Histological validation of high-resolution DTI in human post mortem tissue.

Diffusion tensor imaging (DTI) is amongst the simplest mathematical models available for diffusion magnetic resonance imaging, yet still by far the most used one. Despite the success of DTI as an imaging tool for white matter fibers, its anatomical underpinnings on a microstructural basis remain unclear. In this study, we used 65 myelin-stained sections of human premotor cortex to validate modeled fiber orientations and oft used microstructure-sensitive scalar measures of DTI on the level of individual voxels. We performed this validation on high spatial resolution diffusion MRI acquisitions investigating both white and gray matter. We found a very good agreement between DTI and myelin orientations with the majority of voxels showing angular differences less than 10°. The agreement was strongest in white matter, particularly in unidirectional fiber pathways. In gray matter, the agreement was good in the deeper layers highlighting radial fiber directions even at lower fractional anisotropy (FA) compared to white matter. This result has potentially important implications for tractography algorithms applied to high resolution diffusion MRI data if the aim is to move across the gray/white matter boundary. We found strong relationships between myelin microstructure and DTI-based microstructure-sensitive measures. High FA values were linked to high myelin density and a sharply tuned histological orientation profile. Conversely, high values of mean diffusivity (MD) were linked to bimodal or diffuse orientation distributions and low myelin density. At high spatial resolution, DTI-based measures can be highly sensitive to white and gray matter microstructure despite being relatively unspecific to concrete microarchitectural aspects.

Comparison of Laser Doppler and Laser-Assisted Indocyanine Green Angiography Prediction of Flap Survival in a Novel Modification of the McFarlane Flap

The McFarlane rat ischemic dorsal skin flap model has been commonly used for clinical vector studies, as well as the testing of noninvasive diagnostics. However, variability of this model secondary to flap contact with the wound bed has led many to question its validity. Here we present a novel modification to the McFarlane skin flap using sterile silicone. We also use this model to test the prognostic efficacy of laser-assisted indocyanine green (ICG) angiography and laser Doppler imaging (LDI). A 3 × 9-cm dorsal skin flap with a cranially based pedicle was created, centered 1 cm distal to the scapulae. The flap was undermined, and in one of the 2 groups, a sterile silicone sheet was placed onto the wound bed. All flaps were then reapproximated with sutures 1-cm intervals. Clinical assessment and perfusion imaging was performed immediately postoperative, and at 24, 48, and 72 hours postsurgery. Postoperative day 7 clinical assessment was obtained before euthanasia. A comparative study using silicone blocked versus unblocked models (n = 6 per group) showed that, clinically, both models had equivalent flap survival [8.5 (0.913) vs 9.5 (1.01) cm]. However, a statistically significant increase in perfusion in the mid-third of unblocked models was observed on POD3 [20.28% (2.7%) vs blocked 13.45% (2.5%), P < 0.05], with a similar increase in the distal third on POD7 [18.73% (2.064%) vs 10.91% (4.19%), P < 0.05]. A prognostic study comparing LDI and ICG angiography prediction of POD7 survival at early time points (n = 10) found that LDI underpredicted flap survival at early time points [84.2% (12.03%) on POD0, 87.35% (16.11%) on POD1]. In contrast, ICG was more proficient [100.1% (10.1%) on POD0]. We present a modification of the McFarlane skin flap model that results in similar clinical results, but with a noted reduction in perfusion inconsistencies noted in unblocked models. The ICG angiography is superior to LDI in predicting POD7 flap necrosis within the first 48 hours postinjury. Future work will focus on histologic validation of our model, and vector efficacy testing.

Descriptive epidemiology of 13,038 newly diagnosed and histologically confirmed meningiomas in France: 2006–2010

PurposeThis work describes the clinical epidemiology and pathology for patients undergoing surgery for newly diagnosed meningiomas in France between 2006 and 2010. MethodsThe methodology is based on a multidisciplinary national network previously established by the French Brain Tumor DataBase (FBTDB) (in French: Recensement national histologique des tumeurs primitives du système nerveux central [RnhTPSNC]), and the active participation of the scientific societies involved in neuro-oncology in France. ResultsFrom 2006 to 2010, 13,038 incident cases of meningioma with histological validation were identified and analyzed (9769 women, 3269 men, resection 98.2%, cryopreservation 20.5%). For each histological subtype of meningioma (meningothelial, fibrous, transitional, psammomatous, angiomatous, rare variety, microcystic, secretory, lymphoplasmacyte-rich, clear-cell, chordoid, rhabdoid, metaplastic, atypical, papillary, anaplastic and not otherwise specified), number of cases, sex, median age, cryopreservation and surgery were reported. Among the various histological subtypes, atypical meningioma (grade II) slightly, but significantly, increased after 2007. Headache, sensory-motor impairments and seizures were the most frequent clinical symptoms. Time between the first clinical symptom and surgery ranged from 0 to 314 months, and was <3 months in 37% of cases. At the time of surgery, 9% of patients were asymptomatic. Discussion/conclusionGiven the number of meningiomas not histologically-validated, we can estimate that the gross incidence rate for meningiomas operated in France is about 4.2 per 100,000 person/year. To our knowledge, this work is the most important study evaluating the different subtypes of meningiomas and it validates the relevance of histological databases for central nervous system tumors.

Variables affecting the inter- and intra-examiner reliability of ICDAS for occlusal caries diagnosis in permanent molars.

The aims of this study were to assess the validity and reproducibility of the International Caries Detection and Assessment System (ICDAS) in detecting occlusal caries in permanent molars and to investigate variables that can affect the reproducibility of ICDAS. Five experienced, trained, and calibrated investigators examined the occlusal surfaces of 142 extracted permanent molars, ranging from sound to cavitated dentine caries. All visual examinations were conducted under standard conditions. Examinations were repeated after a period of 1 and 3 months from the initial examination. After all examinations were completed, teeth were sectioned and histologic validation was undertaken. Maximum kappa statistics were used to assess bias among examiners and linear weighted kappa was used to assess inter- and intra-examiners' reproducibility. Sensitivity, specificity, accuracy and area under the receiver operating characteristic curve were obtained at D3 threshold. Differences in the marginal homogeneity were observed for the general dentist. Kappa for intra-examiner reproducibility ranged between 0.66 and 0.81 and the inter-examiner reproducibility ranged between 0.42 and 0.75. ICDAS score of ≥3 presented the best Spearman's correlation coefficient (0.69) at Downer's histologic classification D3. Corresponding sensitivity and specificity values at that level were 0.73 and 0.95, respectively. While variables like the interval of time between teeth examinations did not affect the intra-examiner reproducibility, examiners' specialty influenced inter-examiner's reproducibility over time. ICDAS presented acceptable intra-examiners reproducibility in detecting occlusal caries over time. However, there was a clear effect for examiner's specialty and clinical experience on the inter-examiner's reproducibility of the ICDAS system at different time intervals.

Proximal caries lesion detection using the Canary Caries Detection System: an invitro study.

This study investigated the accuracy of the Canary System (CS) to detect proximal caries lesions invitro, and compared it with conventional methods: International Caries Detection and Assessment System (ICDAS) II and bitewing radiography (BW). Visible proximal surfaces of extracted human teeth were assessed by ICDAS-II before setting them in five manikin mouth models. Then contacting proximal surfaces in mouth models were assessed by BW and CS. Histological validation with polarized-light microscopy served as a gold standard. Pairwise comparisons were performed on area under the curve (AUC), sensitivity, and specificity of the three methods, and corrected using Bonferroni's method. Sensitivities and specificities were compared using a test of proportions and AUC values were compared using DeLong's method. The CS presented significantly higher sensitivity (0.933) than ICDAS-II (0.733, P=0.01) and BW (0.267, P<0.001), and ICDAS-II higher sensitivity than BW (P<0.001). There were no significant differences between their specificity values: 0.825 (CS), 0.65 (ICDAS-II), and 0.875 (BW). The AUC of CS (0.862) was significantly higher than of ICDAS-II (0.681, P<0.001) and BW (0.577, P<0.001). The CS demonstrated greater accuracy in detecting proximal lesions than ICDAS-II and BW, although without significantly higher specificity.

Abstract 295: Magnetic Resonance Imaging Characterization of Peripheral Arterial Chronic Total Occlusions With MicroCT and Histologic Validation

Objectives: Guidelines recommend surgical bypass for peripheral chronic total occlusions (CTOs). Endovascular revascularization, however, offers improved morbidity and shorter length of hospitalization. Not all lesions are amenable to this technique but predicting crossability is difficult due to limitations in characterizing CTOs with current imaging techniques. This study demonstrates the ability of MRI to characterize peripheral CTO components with microCT and histologic validation. Methods: MRI was performed on 15 excised human peripheral arterial CTO segments from 4 patients. Each sample was imaged at 7 Tesla at high resolution (75μm3 voxels) to produce T2- and T2*-maps using ultrashort echo (UTE) sequences with echo times: {20μs, 500μs, 1ms}. A T2* difference image was produced by subtracting the UTE images and a phase map was constructed. The T2, UTE 20μs and T2* difference images were used together to differentiate CTO components. MicroCT and histology were used to validate regions of interest (ROIs). Results: 3 independent reviewers identified 47 ROIs. There was excellent agreement between MRI and microCT for calcium (sensitivity 87%, specificity 99%). There was also good agreement between MRI and histology for adipose tissue (100%, 100%), soft tissue (97%, 97%), thrombus (78%, 100%), collagen (83%, 94%) and open lumen (95%, 98%). Conclusions: These results demonstrate the potential of high-resolution T2 and T2* imaging using UTE, to characterize lesion components in human peripheral CTOs. Further work is required to better differentiate thrombus from collagen. This study provides the foundation for future studies in determining the lesion crossability in CTOs.

29 Synthetic ECV – simplifying ECV quantification by deriving haematocrit from T1 blood

<h3>Background</h3> Extracellular volume (ECV) quantification by cardiovascular magnetic resonance (CMR) measures the extracellular space. Current methodologies require blood haematocrit (Hct) correction, a barrier to easy clinical use. We hypothesised that the relationship between Hct and longitudinal relaxation time of blood (T1_blood) could be calibrated and used to generate a <i>synthetic</i> ECV without Hct. <h3>Methods</h3> 427 subjects with a wide range of health and disease were divided into derivation (n = 214) and validation (n = 213) cohorts (Table 1 for patient characteristics). All subjects underwent T1 mapping with ShMOLLI at 1.5 Tesla for ECV quantification. Venous blood for Hct was obtained prior to scanning with 44 patients having a repeat Hct within 6 h. ECV was calculated as: ECV = (Δ[1/T1_myo] / Δ[1/T1_blood]) * [1-haematocrit]). <i>Synthetic</i> Hct was approximated from the linear relationship between Hct and native T1_blood, and used to calculate <i>synthetic</i> ECV. Histological validation was performed on 18 patients with severe aortic stenosis (age 71 ± 10 years, 78% male). ECV was compared with collagen volume fraction from intra-operative biopsies taken during surgical valve replacement. <h3>Results</h3> In the derivation cohort, native T1_blood and Hct showed a linear relationship (R²=0.45; <i>p &lt; 0.001</i>, Figure 1). This was used to derive <i>synthetic </i>Hct<i> = </i>0.88 – (T1_blood/ 3240). <i>Synthetic </i>ECVcorrelated well with ECV (R² = 0.99; <i>p &lt; 0.001</i>). These results were maintained in the validation cohort. Test:retest variability of haematocrit was higher than expected (n = 44, variability 10% with Hct:Hct R² = 0.86). On histological validation, <i>synthetic </i>and conventional ECV both correlated well with collagen volume fraction (R² = 0.61 and 0.69, <i>p &lt; 0.001</i>). <h3>Conclusion</h3> <i>Synthetic </i>ECV allows instantaneous non-invasive quantification of the myocardial extracellular space without blood sampling. Inline application of <i>synthetic</i> ECV may be an attractive alternative in clinical practice.

Optical Coherence Tomography to Optimize Stent Deployment: Seeing is Believing

Optimal coherence tomography (OCT) is a new light-based intracoronary imaging modality with unprecedented spatial resolution. Currently, its axial resolution is only 15 mm, that is, 10 times higher than that of more classical techniques such as intravascular ultrasound (IVUS) based on ultrasounds (150 mm). Optimal coherence tomography therefore provides extremely high-quality images of the coronary wall, especially of the structures closest to the vessel lumen. Moreover, numerous studies with histological validation have confirmed its ability to adequately differentiate the distinct types of atheromatous plaque, including fibrous plaques (homogeneous, signal-rich regions), lipid plaque (progressively signal-poor regions) and calcified plaque (signal poor, sharp border lesions). For the first time, OCT allows precise measurement of the thickness of the fibrous cap covering the lipid cores and in vivo diagnosis of the presence of thin-cap fibroatheromas. Similarly, this technique can identify the characteristic signs produced by the accumulation of macrophages and cholesterol crystals in the vessel wall, as well as the presence of small ruptures of the intima and of intracoronary thrombi that could not be visualized with IVUS until now. All these properties explain the enormous attractiveness of this technique in the characterization of vulnerable plaques and in the study of the micromorphology of plaques that have already developed a complication. However, the penetration of OCT in the vessel wall is limited and consequently visualization of structures beyond the lumen (near the adventitia) is compromised when there is a substantial amount of atheromatous plaque. Equally, OCT cannot penetrate through red thrombi (fibrin-rich), which produce an intense posterior shadow. Therefore, OCT is not suitable for measuring the total volume of atheromatous plaque. To do this, IVUS remains the technique of choice when the aim is to study the progression or regression of coronary atherosclerosis. From a practical point of view, with the initial technology (time domain), image acquisition was relatively slow and, due to the need to completely eliminate blood from the interior of the

Native T1 mapping in patients with idiopathic dilated cardiomyopathy for the assessment of diffuse myocardial fibrosis: validation against histologic endomyocardial biopsy

Background Late gadolinium enhancement (LGE) MRI provides a significant impact on prognosis in dilated cardiomyopathy (DCM) patients. However, LGE MRI is less suitable for quantifying the degree of fibrosis in diffusely diseased myocardium. T1 mapping technique allows for the quantitative assessment of extracellular volume fraction (ECV), which has been histologically validated against the collagen volume fraction (CVF). Native myocardial T1 also has a potential for the noninvasive detection of myocardial fibrosis. Recent study demonstrated that native myocardial T1 permits the discrimination between normal and diffusely diseased myocardium accurately in DCM patients. However, in-vivo histological validation of native myocardial T1 in DCM patients is still lacking. The aim of this study was to histologically validate native myocardial T1 for the assessment of diffuse myocardial fibrosis in DCM patients.

MRI characterization of peripheral arterial chronic total occlusions at 7 Tesla with microCT and histologic validation

Background Current treatment guidelines recommend surgical bypass for peripheral chronic total occlusions (CTOs)[1]. Percutaneous transluminal angioplasty (PTA), however, offers a less invasive approach with improved perioperative morbidity, shorter length of hospital stay, and lower cost[2]. Not all lesions are amenable to this technique and there is a significant primary failure rate[2]. Predicting lesion crossability is difficult because current imaging techniques offer limited information with which to characterize CTOs. The ability to distinguish between hard and soft biological substances that compose a CTO can aid procedural planning and facilitate intervention. This pilot study demonstrates the ability of high resolution MRI to characterize peripheral CTO components with microCT and histologic validation.

Myocardial scar surface area identified by LGE MRI is an independent predictor of mortality in post-infarction patients

Background Recent research has shown that the size of myocardial gray zone (a mixture of normal and infarcted tissue) identified from late gadolinium enhanced (LGE) MRI is an independent predictor of adverse cardiac events in post-infarction patients. However, definition of myocardial gray zone in LGE images (e.g. using the N-STD method) remains difficult for varying MR protocols and qualities, lacks histological validation, and may lead to conflicting conclusions. We sought to establish a novel predictive scar parameter independent of gray zone definition.

Multimodal Imaging in Lung Cancer: It Is Time to Change

The imaging techniques can be classified into two main groups: Structural/morphological imaging (SMI), which includes X rays (XR), computed tomography (CT), ultrasounds (US) as well as some varieties of magnetic resonance (MRI), and shows anatomic-morphological aspects, and molecular imaging (MI), which includes nuclear medicine (SPECT, PET), fMRI, optical and nanosystems techniques, and provides information about biochemistry/biological activity, often before structural changes. According to Society of Nuclear Medicine and Molecular Imaging, MI “is the visualization, characterization, and measurement of biological processes at the molecular and cellular levels in humans and other living systems”. MI procedures are noninvasive, safe and painless. Its sensitivity is greater than SMI, but it lacks anatomical detail, which has led to the development of multimodal imaging, combining structural and molecular techniques, widely used at present in daily practice. The pillars of MI are biochemistry/biology, instrumentation and software, and its cycle is the following: study of biology/biochemistry of a process, establishment/definition of specific targets, and development of tracers, preclinical imaging, histological validation and finally clinical imaging. This new concept led to the individualized diagnostic and treatment, being the patient the center of the medical activity. “As opposed to the doctor-centric, curative model of the past, the future is going to be patient-centric and proactive” said Dr. Zerhouni (NIH Medline Plus Winter 2007). The doctor must adapt to the needs of the own patient and this fact requires a true change of heart, because MI is intimately tied to the biology of the disease to analyzing. A new and strong interrelationship came into being: a bidirectional system biology-imaging that will allow to be much more effective in the daily practice, not only in relation to diagnosis (specific and early), but also with therapy (guide cancer treatment selection and evaluate early treatment response). There is an absolute necessity to lock the two together. Likewise, in the future the biology of a disease will indicate us what is the most adequate imaging technique and vice versa. In this regard, we know that in non-small cell lung cancer (NSCLC), ALK+ status is associated with distinct characteristics at CT imaging (CT radiogenomic characterization) [1], and that in lung adenocarcinomas 18F-FDG uptake values are related with expression levels of cellular Glucose Transporters and EGFR mutations. For this reason, different EGFR mutations correlate with different FDG uptake values.

Histologic validation of vacuum sealed, formalin-free tissue preservation, and transport system.

We describe five validation trials of new vacuum sealing technologies that change the approach to the preanalytic "front end" of specimen transport, handling, and processing and illustrate their adaptation and integration into existing Lean laboratory operations with reduction in formalin use and personnel exposure to this toxic and potentially carcinogenic fixative. These trials provide histologic assessment by numerous pathologists of tissues processed in this new paradigm and define the financial advantages of applying this technology to the postanalytic or "back end" process of tissue storage. We conclude that the TisssueSAFE and SealSAFE vacuum sealing systems are both promising technologies for preserving fresh human specimens that can promote a safer environment by markedly reducing formalin use in operating room theaters and can minimize formalin use by laboratories.

Optimization, validation and efficacy of the phytohaemagglutinin inflammation assay for use in ecoimmunological studies of amphibians.

The global amphibian biodiversity crisis is driven by disease, habitat destruction and drastically altered ecosystems. It has given rise to an unprecedented need to understand the link between rapidly changing environments, immunocompetence and wildlife health (the nascent field of ecoimmunology). Increasing our knowledge of the ecoimmunology of amphibians necessitates the development of reliable, field-applicable methods of assessing immunocompetence in non-model species. The phytohaemagglutinin (PHA) inflammation assay uses a lectin to elicit localized inflammation that reflects an organism's capacity to mount an immune response. Although extensively used in birds to assess responses to environmental change, stress and disease, its application in amphibians has been extremely limited. We developed, validated and optimized a practical and effective phytohaemagglutinin inflammation assay in phylogenetically distant amphibians and demonstrated its suitability for use in a wide range of ecoimmunological studies. The protocol was effective for all species tested and worked equally well for both sexes and for adult and sub-adult animals. We determined that using set-force-measuring instruments resulted in a 'compression effect' that countered the inflammatory response, reinforcing the need for internal controls. We developed a novel method to determine peak response times more accurately and thereby improve assay sensitivity. Histological validation demonstrated considerable interspecies variation in the robustness of amphibian immune defences. Importantly, we applied the assay to a real-world scenario of varying environmental conditions and proved that the assay effectively detected differences in immune fitness between groups of animals exposed to ecologically meaningful levels of density stress. This provided strong evidence that one cost of metamorphic plasticity responses by tadpoles to increasing density is a reduction in post-metamorphic immune fitness and that metamorphosis does not prevent phenotypic carry-over of larval stress to the adult phenotype. This assay provides an effective tool for understanding the role of global environmental change in the amphibian extinction crisis.

A phase I feasibility study of multi-modality imaging assessing rapid expansion of marrow fat and decreased bone mineral density in cancer patients

PurposeCancer survivors are at an increased risk for fractures, but lack of effective and economical biomarkers limits quantitative assessments of marrow fat (MF), bone mineral density (BMD) and their relation in response to cytotoxic cancer treatment. We report dual energy CT (DECT) imaging, commonly used for cancer diagnosis, treatment and surveillance, as a novel biomarker of MF and BMD. MethodsWe validated DECT in pre-clinical and phase I clinical trials and verified with water–fat MRI (WF-MRI), quantitative CT (QCT) and dual-energy X-ray absorptiometry (DXA). Basis material composition framework was validated using water and small-chain alcohols simulating different components of bone marrow. Histologic validation was achieved by measuring percent adipocyte in the cadaver vertebrae and compared with DECT and WF-MRI. For a phase I trial, sixteen patients with gynecologic malignancies (treated with oophorectomy, radiotherapy or chemotherapy) underwent DECT, QCT, WF-MRI and DXA before and 12months after treatment. BMD and MF percent and distribution were quantified in the lumbar vertebrae and the right femoral neck. ResultsMeasured precision (3mg/cm3) was sufficient to distinguish test solutions. Adiposity in cadaver bone histology was highly correlated with MF measured using DECT and WF-MRI (r=0.80 and 0.77, respectively). In the clinical trial, DECT showed high overall correlation (r=0.77, 95% CI: 0.69, 0.83) with WF-MRI. MF increased significantly after treatment (p<0.002). Chemotherapy and radiation caused greater increases in MF than oophorectomy (p<0.032). L4 BMD decreased 14% by DECT, 20% by QCT, but only 5% by DXA (p<0.002 for all). At baseline, we observed a statistically significant inverse association between MF and BMD which was dramatically attenuated after treatment. ConclusionOur study demonstrated that DECT, similar to WF-MRI, can accurately measure marrow adiposity. Both imaging modalities show rapid increase in MF following cancer treatment. Our results suggest that MF and BMD cannot be used interchangeably to monitor skeletal health following cancer therapy.

Label-free intraoperative parathyroid localization with near-infrared autofluorescence imaging.

The inability to accurately localize the parathyroid glands during parathyroidectomy and thyroidectomy procedures can prevent patients from achieving postoperative normocalcemia. There is a critical need for an improved intraoperative method for real-time parathyroid identification. The objective of the study was to test the accuracy of a real-time, label-free technique that uses near-infrared (NIR) autofluorescence imaging to localize the parathyroid. The study was conducted at the Vanderbilt University endocrine surgery center. Patients undergoing parathyroidectomy and/or thyroidectomy were included in this study. To validate the intrinsic fluorescence signal in parathyroid, point measurements from 110 patients were collected using NIR fluorescence spectroscopy. Fluorescence imaging was performed on 6 patients. Imaging contrast is based on a previously unreported intrinsic NIR fluorophore in the parathyroid gland. The accuracy of fluorescence imaging was analyzed in comparison with visual assessment and histological findings. The detection rate of parathyroid glands was measured. The parathyroid glands in 100% of patients measured with fluorescence imaging were successfully detected in real time. Fluorescence images consistently showed 2.4 to 8.5 times higher emission intensity from the parathyroid than surrounding tissue. Histological validation confirmed that the high intrinsic fluorescence signal in the parathyroid gland can be used to localize the parathyroid gland regardless of disease state. NIR fluorescence imaging represents a highly sensitive, real-time, label-free tool for parathyroid localization during surgery. The elegance and effectiveness of NIR autofluorescence imaging of the parathyroid gland makes it highly attractive for clinical application in endocrine surgery.

Delayed contrast extravasation MRI: a new paradigm in neuro-oncology.

Conventional magnetic resonance imaging (MRI) is unable to differentiate tumor/nontumor enhancing tissues. We have applied delayed-contrast MRI for calculating high resolution treatment response assessment maps (TRAMs) clearly differentiating tumor/nontumor tissues in brain tumor patients. One hundred and fifty patients with primary/metastatic tumors were recruited and scanned by delayed-contrast MRI and perfusion MRI. Of those, 47 patients underwent resection during their participation in the study. Region of interest/threshold analysis was performed on the TRAMs and on relative cerebral blood volume maps, and correlation with histology was studied. Relative cerebral blood volume was also assessed by the study neuroradiologist. Histological validation confirmed that regions of contrast agent clearance in the TRAMs >1 h post contrast injection represent active tumor, while regions of contrast accumulation represent nontumor tissues with 100% sensitivity and 92% positive predictive value to active tumor. Significant correlation was found between tumor burden in the TRAMs and histology in a subgroup of lesions resected en bloc (r(2) = 0.90, P < .0001). Relative cerebral blood volume yielded sensitivity/positive predictive values of 51%/96% and there was no correlation with tumor burden. The feasibility of applying the TRAMs for differentiating progression from treatment effects, depicting tumor within hemorrhages, and detecting residual tumor postsurgery is demonstrated. The TRAMs present a novel model-independent approach providing efficient separation between tumor/nontumor tissues by adding a short MRI scan >1 h post contrast injection. The methodology uses robust acquisition sequences, providing high resolution and easy to interpret maps with minimal sensitivity to susceptibility artifacts. The presented results provide histological validation of the TRAMs and demonstrate their potential contribution to the management of brain tumor patients.

NI-85 * DELAYED CONTRAST MRI FOR DIFFERENTIATING TUMOR/NON-TUMOR TISSUES IN BRAIN TUMOR PATIENTS - HISTOLOGICAL VALIDATION AND COMPARISON WITH DSC/DCE

BACKGROUND: Conventional MRI is unable to differentiate tumor/non-tumoral enhancing tissues on conventional T1-MRI (radionecrosis/pseudoprogression). We have applied delayed contrast MRI for calculating high resolution (1mm3) treatment response assessment maps (TRAMs) clearly differentiating tumor/non-tumoral tissues in brain tumor patients and validated the TRAMs histologically. We further assessed the sensitivity and positive predictive value (PPV) of rCBV/KTrans (DSC/DCE MRI) to tumor. METHODS: 162 patients with primary/metastatic tumors were recruited/followed on study. The maps were validated by comparing pre-surgical maps of 51 patients with histology. Histological evaluation consisted of blinded pathological reports and non-blinded evaluation of 62 biopsies and 8 en-block samples. The sensitivity/PPV of rCBV to tumor was studied for 46 resected patients, where rCBV was compared with histology. The sensitivity/PPV of rCBV/KTranse was studied separately for 49/42 non-resected patients where these parameters were compared with the TRAMs. RESULTS: Histological validation confirmed that regions of contrast agent-clearance > 1hr post contrast injection represent morphologically active tumor while regions of contrast accumulation represent non-tumor tissues. Based on the blinded histological reports, the TRAMs showed sensitivity/PPV to active tumor of 100%/92%. The addition of the non-blinded data resulted in sensitivity/PPV of 99%/95%. Significant correlation was found between tumor volumes in the TRAMs and in the en-block samples (r2 = 0.84, p < 0.0001). Comparison of rCBV with histology resulted in sensitivity/PPV of 51%/96%. When comparing rCBV/KTrans to the TRAMs we found a sensitivity of 23%/24% and PPV of 100%/90% to tumor regions in the TRAMs. The lower sensitivity of rCBV to tumor in the non-resected patients may be attributed to the larger percentage of smaller metastatic tumors that tend towards lower perfusion. CONCLUSIONS: Despite the high PPV of rCBV/KTrans to tumor, the low sensitivity suggests that 49%-76% of the tumors will remain undetected. Our data suggest that the TRAMs provide both high PPV and high sensitivity to tumor tissues.

Cancer imaging in the era of precision treatment: present and future

Cancer imaging in the era of precision treatment: present and future

Consequences of the natural course of articular osteochondrosis in pigs for the suitability of computed tomography as a screening tool.

BackgroundA significant heritability has been documented for articular osteochondrosis. Selection against osteochondrosis has historically been based on macroscopic evaluation, but as computed tomography (CT) now is used to select boars with optimal body composition it can potentially also be used to screen for osteochondrosis. False negative diagnosis will occur if defects have not developed or have resolved prior to screening at a single time point.The aim of the current study was to assess the suitability of the use of CT at a single point in time as a screening tool in piglets for articular osteochondrosis, which is known to be a highly dynamic condition in which lesions develop and resolve over time.MethodsMale Landrace piglets (n = 18) were serial CT scanned from 2–8 times at biweekly intervals from 70–180 days of age. At each interval, 1–2 piglets were euthanased and the left distal femur processed for histological validation.ResultsA total of 795 defects were identified in the 112 available CT scans. Within the hind and fore limbs, the incidence of defects was highest in the stifle (n = 321) and elbow joints (n = 110), respectively. Ninety-eight per cent of the defects in the stifle and elbow joints had developed by the 7th examination interval when the piglets were a mean age of 159 days old. The proportion of defects that resolved was lowest in the stifle joint at 51% and highest in the elbow joint at 69%.ConclusionsScanning of the current piglets at an age of 159 days resulted in detection of 98% of the total number of defects that developed up to the maximum age of 180 days. The proportion of defects that resolved ranged from 51–69% for different joints, but may not adversely affect prevalence as this category of false negative diagnosis will result in selection of pigs that are disposed for healing. Optimally timed CT is a powerful screening tool for osteochondrosis.