Lesion Of Interest Research Articles

Targeted stereology: sampling heterogeneously distributed structures and lesions in the lung

Stereology, the gold standard of lung morphometry, critically depends on sampling of tissue for analysis. Random sampling approaches guarantee each part of the organ an equal chance of being included in the analysis; hence, they guarantee a representative sample of the whole. However, when biological or pathological structures of interest are rare and/or heterogeneously distributed over the whole lung, the random sampling approach can be inefficient or even result in meaningless data. In such cases, a targeted sampling approach can be useful, which helps to relate the analytical items to an appropriate reference space. Targeted stereology greatly benefits from the increasing availability of multiresolution imaging techniques at macroscopic and microscopic levels as well as digital tools of segmentation. As such, this article outlines two basic sampling scenarios: 1) In the first scenario, computed tomography and microscopy are subsequently used to segment the airway/arterial tree and perform stereological measurements on specific branches of the tree. 2) The second scenario deals with the heterogeneous distribution of pathological lesions. This type of analysis can be divided into two stages: assessment of lesions of interest (LOIs) within the lung and assessment of subcompartments within LOIs. Taken together, targeted stereology has a thorough foundation in stereological theory and is able to not only significantly increase the efficiency of the analysis but also yield new types of information that would be lost with the classical random sampling approach.

Prospective comparison of [18F]AlF-NOTA-octreotide PET/MRI to [68Ga]Ga-DOTATATE PET/CT in neuroendocrine tumor patients

BackgroundFluorine-18-labeled SSAs have the potential to become the next-generation tracer in SSTR-imaging in neuroendocrine tumor (NET) patients given their logistical advantages over the current gold standard gallium-68-labeled SSAs. In particular, [18F]AlF-OC has already shown excellent clinical performance. We demonstrated in our previous report from our prospective multicenter trial that [18F]AlF-OC PET/CT outperforms [68Ga]Ga-DOTA-SSA, but histological confirmation was lacking due to ethical and practical reasons. In this second arm, we therefore aimed to provide evidence that the vast majority of [18F]AlF-OC PET lesions are in fact true NET lesions by analyzing their MR characteristics on simultaneously acquired MRI. We had a special interest in lesions solely detected by [18F]AlF-OC (“incremental lesions”).MethodsTen patients with a histologically confirmed neuroendocrine tumor (NET) and a standard-of-care [68Ga]Ga-DOTATATE PET/CT, performed within 3 months, were prospectively included. Patients underwent a whole-body PET/MRI (TOF, 3 T, GE Signa), 2 hours after IV injection of 4 MBq/kg [18F]AlF-OC. Positive PET lesions were evaluated for a corresponding lesion on MRI. The diagnostic performance of both PET tracers was evaluated by determining the detection ratio (DR) for each scan and the differential detection ratio (DDR) per patient.ResultsIn total, 195 unique lesions were detected: 167 with [68Ga]Ga-DOTATATE and 193 with [18F]AlF-OC. The DR for [18F]AlF-OC was 99.1% versus 91.4% for [68Ga]Ga-DOTATATE, significant for non-inferiority testing (p = 0.0001). Out of these 193 [18F]AlF-OC lesions, 96.2% were confirmed by MRI to be NET lesions. Thirty-three incremental lesions were identified by [18F]AlF-OC, of which 91% were confirmed by MRI and considered true positives.ConclusionThe DR of [18F]AlF-OC was numerically higher and non-inferior to the DR of [68Ga]Ga-DOTATATE. [18F]AlF-OC lesions and especially incremental lesions were confirmed as true positives by MRI in more than 90% of lesions. Taken together, these data further validate [18F]AlF-OC as a new alternative for SSTR PET in clinical practice.Trial registration ClinicalTrials.gov: NCT04552847. Registered 17 September 2020, https://beta.clinicaltrials.gov/study/NCT04552847

Magnetic resonance imaging radiomic features for recurrent prostate cancer following proton radiation therapy-A pilot study.

The role of multiparametric MRI (mp-MRI) for postproton radiation evaluation is unclear. In this pilot study, we characterize the mp-MRI features using the Prostate Imaging-Reporting and Data System (PI-RADS) for recurrent prostate cancer (PCa) following proton radiation therapy. After obtaining IRB approval, we identified 163 consecutive cases who underwent MRI-fusion prostate biopsy at our institution from November 2017 to May 2020. This study evaluated patients with prostate cancer (PCa) with biochemical recurrence following proton radiation. Patients were excluded if they had grossly metastatic disease, metal fragments, implanted devices, or with surgically removed prostates. The mpMRI studies were reviewed in depth and scored by 2 fellowship-trained radiologists. Following MRI-fusion biopsy of lesions of interest (LOI), slides were read by fellowship-trained pathologists. We found 14 patients with 16 lesions who met the study inclusion criteria. The median age was 69 years (range 57-79) and median time to biochemical recurrence was 7.3 years (range 3-13). On post-treatment imaging, decreases in prostate size and diffusely decreased T2 signal intensity were observed, making the use of apparent diffusion coefficient (ADC) and early enhancement at dynamic contrast enhanced (DCE) imaging often necessary for diagnosis of disease recurrence. We identified a total of 16 lesions with PIRADS scores of 3 or higher. Of these lesions, there were 5 PIRADS 3 lesions (4/5 (80%) without prostate cancer), 7 PIRADS 4-5 lesions (6 (86%) had high risk Pca), and 4 lesions with unassigned PIRADS scores (100% had high risk cancers). Among the MRI variables, diffusion weighted imaging (DWI) heterogeneity had the strongest association with recurrence of PCa (P < 0.001). Results of our pilot study showed that the PIRADS scoring system in the postproton radiation therapy setting has some correlations with prostate cancer recurrence; However, the clinical value of these findings are unclear. While definitive PIRADS categorization of lesions demonstrated expected frequency of cancer consistent with the scoring system, all unassigned lesions also harbored malignancy suggesting a cautious approach to PIRADS scoring system in postproton radiation setting. The findings from this study may be validated using a larger cohort.

Pathologic correlates of the magnetization transfer ratio in multiple sclerosis.

To identify pathologic correlates of magnetization transfer ratio (MTR) in multiple sclerosis (MS) in an MRI-pathology study. We acquired MTR maps at 3T from 16 fixed MS brains and 4 controls, and immunostained 100 tissue blocks for neuronal neurofilaments, myelin (SMI94), tissue macrophages (CD68), microglia (IBA1), B-lymphocytes, T-lymphocytes, cytotoxic T-lymphocytes, astrocytes (glial fibrillary acidic protein), and mitochondrial damage (COX4, VDAC). We defined regions of interest in lesions, normal-appearing white matter (NAWM), and cortical normal-appearing gray matter (NAGM). Associations between MTR and immunostaining intensities were explored using linear mixed-effects models (with cassettes nested within patients) and interaction terms (for differences between regions of interest and between cases and controls); a multivariate linear mixed-effects model identified the best pathologic correlates of MTR. MTR was the lowest in white matter (WM) lesions (23.4 ± 9.4%) and the highest in NAWM (38.1 ± 8.7%). In MS brains, lower MTR was associated with lower immunostaining intensity for myelin (coefficient 0.31; 95% confidence interval [CI] 0.07-0.55), macrophages (coefficient 0.03; 95% CI 0.01-0.07), and astrocytes (coefficient 0.51; 95% CI 0.02-1.00), and with greater mitochondrial damage (coefficient 0.31; 95% CI 0.07-0.55). Based on interaction terms, MTR was more strongly associated with myelin in WM (coefficient 1.58; 95% CI 1.09-2.08) and gray matter (GM) lesions (coefficient 0.66; 95% CI 0.13-1.20), and with macrophages (coefficient 1.40; 95% CI 0.56-2.25), astrocytes (coefficient 2.66; 95% CI 1.31-4.01), and mitochondrial damage (coefficient -12.59; 95% CI -23.16 to -2.02) in MS brains than controls. In the multivariate model, myelin immunostaining intensity was the best correlate of MTR (coefficient 0.31; 95% CI 0.09-0.52; p = 0.004). Myelin was the strongest correlate of MTR, especially in WM and cortical GM lesions, but additional correlates should be kept in mind when designing and interpreting MTR observational and experimental studies in MS.

Kinetic modeling of 68Ga-PSMA-11 and validation of simplified methods for quantification in primary prostate cancer patients

BackgroundThe positron emission tomography (PET) ligand 68Ga-Glu-urea-Lys(Ahx)-HBED-CC (68Ga-PSMA-11) targets the prostate-specific membrane antigen (PSMA), upregulated in prostate cancer cells. Although 68Ga-PSMA-11 PET is widely used in research and clinical practice, full kinetic modeling has not yet been reported nor have simplified methods for quantification been validated. The aims of our study were to quantify 68Ga-PSMA-11 uptake in primary prostate cancer patients using compartmental modeling with arterial blood sampling and to validate the use of standardized uptake values (SUV) and image-derived blood for quantification.ResultsFifteen patients with histologically proven primary prostate cancer underwent a 60-min dynamic 68Ga-PSMA-11 PET scan of the pelvis with axial T1 Dixon, T2, and diffusion-weighted magnetic resonance (MR) images acquired simultaneously. Time-activity curves were derived from volumes of interest in lesions, normal prostate, and muscle, and mean SUV calculated. In total, 18 positive lesions were identified on both PET and MR. Arterial blood activity was measured by automatic arterial blood sampling and manual blood samples were collected for plasma-to-blood ratio correction and for metabolite analysis. The analysis showed that 68Ga-PSMA-11 was stable in vivo. Based on the Akaike information criterion, 68Ga-PSMA-11 kinetics were best described by an irreversible two-tissue compartment model. The rate constants K1 and k3 and the net influx rate constants Ki were all significantly higher in lesions compared to normal tissue (p < 0.05). Ki derived using image-derived blood from an MR-guided method showed excellent agreement with Ki derived using arterial blood sampling (intraclass correlation coefficient = 0.99). SUV correlated significantly with Ki with the strongest correlation of scan time-window 30–45 min (rho 0.95, p < 0.001). Both Ki and SUV correlated significantly with serum prostate specific antigen (PSA) level and PSA density.Conclusions68Ga-PSMA-11 kinetics can be described by an irreversible two-tissue compartment model. An MR-guided method for image-derived blood provides a non-invasive alternative to blood sampling for kinetic modeling studies. SUV showed strong correlation with Ki and can be used in routine clinical settings to quantify 68Ga-PSMA-11 uptake.

Microvascular invasion in hepatocellular carcinoma: is it predictable with quantitative computed tomography parameters?

Objective To investigate whether quantitative computed tomography (CT) measurements can predict microvascular invasion (MVI) in hepatocellular carcinoma (HCC).Materials and Methods This was a retrospective analysis of 200 cases of surgically proven HCCs in 125 consecutive patients evaluated between March 2010 and November 2017. We quantitatively measured regions of interest in lesions and adjacent areas of the liver on unenhanced CT scans, as well as in the arterial, portal venous, and equilibrium phases on contrast-enhanced CT scans. Enhancement profiles were analyzed and compared with histopathological references of MVI. Univariate and multivariate logistic regression analyses were used in order to evaluate CT parameters as potential predictors of MVI.Results Of the 200 HCCs, 77 (38.5%) showed evidence of MVI on histopathological analysis. There was no statistical difference between HCCs with MVI and those without, in terms of the percentage attenuation ratio in the portal venous phase (114.7 vs. 115.8) and equilibrium phase (126.7 vs. 128.2), as well as in terms of the relative washout ratio, also in the portal venous and equilibrium phases (15.0 vs. 8.2 and 31.4 vs. 26.3, respectively).Conclusion Quantitative dynamic CT parameters measured in the preoperative period do not appear to correlate with MVI in HCC.

A dual modeling approach to automatic segmentation of cerebral T2 hyperintensities and T1 black holes in multiple sclerosis.

Background and purposeMagnetic resonance imaging (MRI) is crucial for in vivo detection and characterization of white matter lesions (WML) in multiple sclerosis (MS). The most widely established MRI outcome measure is the volume of hyperintense lesions on T2-weighted images (T2L). Unfortunately, T2L are non-specific for the level of tissue destruction and show a weak relationship to clinical status. Interest in lesions that appear hypointense on T1-weighted images (T1L) (“black holes”) has grown because T1L provide more specificity for axonal loss and a closer link to neurologic disability. The technical difficulty of T1L segmentation has led investigators to rely on time-consuming manual assessments prone to inter- and intra-rater variability. This study aims to develop an automatic T1L segmentation approach, adapted from a T2L segmentation algorithm.Materials and methodsT1, T2, and fluid-attenuated inversion recovery (FLAIR) sequences were acquired from 40 MS subjects at 3 Tesla (3 T). T2L and T1L were manually segmented. A Method for Inter-Modal Segmentation Analysis (MIMoSA) was then employed.ResultsUsing cross-validation, MIMoSA proved to be robust for segmenting both T2L and T1L. For T2L, a Sørensen-Dice coefficient (DSC) of 0.66 and partial AUC (pAUC) up to 1% false positive rate of 0.70 were achieved. For T1L, 0.53 DSC and 0.64 pAUC were achieved. Manual and MIMoSA segmented volumes were correlated and resulted in 0.88 for T1L and 0.95 for T2L. The correlation between Expanded Disability Status Scale (EDSS) scores and manual versus automatic volumes were similar for T1L (0.32 manual vs. 0.34 MIMoSA), T2L (0.33 vs. 0.32), and the T1L/T2L ratio (0.33 vs 0.33).ConclusionsThough originally designed to segment T2L, MIMoSA performs well for segmenting T1 black holes in patients with MS.

Application values of 3.0T magnetic resonance diffusion weighted imaging for distinguishing liver malignant tumors and benign lesions.

The aim of the present study was to investigate the significance and values of 3.0T diffusion weighted imaging (DWI) to differentially diagnose benign and malignant space-occupying liver lesions. A total of 91 patients with liver space-occupying lesions (145 lesions) were admitted into Zhongnan Hospital of Wuhan University (Wuhan, China) from November 2015 to May 2016. Routine scanning, DWI and high-resolution T2-weighted imaging using spin-echo echo-planar imaging were performed on all patients, to compare the apparent diffusion coefficient (ADC) values of three regions of interest in lesions with normal liver tissue. The ADC values of malignant liver lesions compared with benign liver cysts demonstrated a statistically significant difference in low b-value (P<0.05) and there was also a significant difference between malignant lesion and hepatic cyst, hepatic hemangioma or hepatic abscess in middle b-value (P<0.05). The measured ADC value may be more conducive to identify the nature of the liver space-occupying lesions; as the ADC values of malignant liver lesion, liver cyst, and liver abscesses demonstrated a statistical significance in high b-value (P<0.05). The mean ADC values between malignant liver tumors compared with benign lesions indicated a statistically significant difference. In the present study, liver space-occupying lesions demonstrated different DWI features and ADC ranges, and 3.0T DWI may be a potential means to accurately determine the nature of lesions, identifying benign and malignant space-occupying lesions.

Utility of prostate multiparametric MRI (mpMRI) for recurrent prostate cancer after radiation therapy and cryotherapy.

71 Background: We evaluated the accuracy of mpMRI for identifying locally recurrent prostate cancer after primary radiotherapy and cryotherapy. Methods: Between 2009-2015, 61 patients with evidence of rising PSA after external-beam radiotherapy (EBRT) (N = 33), brachytherapy (N = 6), and cryotherapy (N = 22) were evaluated for locally recurrent prostate cancer with mpMRI and prostate biopsy. Of these patients, 6 (10%) received androgen deprivation therapy (ADT) in combination with EBRT for a median of 24 months. Three of the cryotherapy patients received prior EBRT. Patients were identified from a prospective mpMRI database. All patients with a lesion of interest (LOI) underwent a ≥ 12-core, post-mpMRI cognitive fusion prostate biopsy. We excluded 16 patients with mpMRI who did not undergo prostate biopsy (5 positive, 11 negative). Results: Median age was 70 (IQR: 64-77). The median time from primary treatment to mpMRI was 5 years (IQR: 3-9) and the median PSA at mpMRI was 3.6 ng/mL (IQR: 2.1-5.5). Median prostate volume was 18.8 cc (IQR: 11.0-28.0 cc). mpMRI revealed lesions of interest (LOI) in 39 (64%) and 41 (67%) had biopsy-proven local recurrence. Of the 22 patients with negative mpMRI, 8 (36%) had a positive biopsy, with a median prostate volume of 19 cc, median maximum cancer length of 5 mm, median PSA of 2.5 and biopsy Gleason scores 3+3 (N = 1), 4+3 (N=2), 5+4 (N = 1), 5+5 (N = 1) and ungraded due to treatment effect (N = 3). Of the 39 patients with LOI on mpMRI, 33 (85%) had a positive biopsy. Table 1 summarizes the mpMRI and biopsy results. The sensitivity, specificity, PPV and NPV of mpMRI to predict cancer diagnosis at biopsy was 80.5%, 70.0%, 84.6% and 63.6%, respectively. On univariate analysis, gland size (p=0.367), PSA (p=0.872), biopsy Gleason score (p=0.892) and primary treatment modality (p=0.177) did not significantly predict discrepancy between mpMRI and biopsy findings. Conclusions: mpMRI reliably identifies prostate cancer recurrence after primary radiation therapy and cryoablation. [Table: see text]

PD34-01 MR-US FUSION BIOPSY VS. TRUS SATURATION PROSTATE BIOPSY IN ACTIVE SURVEILLANCE

INTRODUCTION AND OBJECTIVES: MR-US fusion biopsy (MR-US-FB) represents a potentially useful tool to assess for PCa progression in patients on active surveillance (AS). It is unknown whether MR-US-FB is superior to TRUS saturation biopsy to accurately characterize disease reclassification. We analyzed our initial experience with MR-US-FB compared with TRUS saturation biopsy in patients on AS. METHODS: 90 patients undergoing surveillance biopsy were analyzed. 35 patients with previously diagnosed PCa on active surveillance underwent MR-US-FB (UroNav, Invivo) with standard 12-core TRUS biopsy in same procedure from 7/2014-10/2014. Patients first had multiparametric prostate MRI (3T without endorectal coil) and target lesions of interest (LOI) for biopsy were marked. Median number of LOI/ patient was 2. Median number of cores per LOI was 3. These patients were compared to a cohort of 55 patients from 2011-2013 undergoing saturation ( 20 cores) TRUS biopsy as part of an active surveillance protocol. RESULTS: Overall, there was no difference between groups in cancer detection or reclassification (p>0.05). Results summarized in table below. The mean total number of cores was higher with saturation biopsy vs. MR-US-FB (20 1.5 vs. 18 5.4, p<.001). Number of previous biopsies was higher in the MR fusion group: (2.0 1.3 vs. 1.4 0.6, p1⁄40.02). Median PSA was 4.3 (IQR 3-6) in the MR fusion group vs. 5.6 (IQR 3.5-7.5) in the saturation biopsy group (p1⁄40.07.). Multivariable analysis of age, PSA, number of previous biopsies, biopsy type (MR vs. saturation), or total number of cores taken demonstrated no significant relationship with PCa diagnosis. 7/35 of MR biopsies showed PCa in both target and standard cores. Of these, 2 had no difference in Gl grade, 4 had higher Gl grade in the standard cores, and only 1 had higher Gl grade in target core. 16/35 patients had PCa present in standard cores only (2 of these were Gl 7). One patient had PCa in only targeted cores, and one patient had only target cores taken. CONCLUSIONS: There was no difference in rates of cancer detection, risk group reclassification, or reclassification by Gleason score upgrading between MR-US-FB and TRUS saturation biopsy in patients on AS. The majority of patients undergoing MR-US-FB had no Gleason upgrading when comparing cancer in standard TRUS cores to cores taken from target lesions.

Mediastinal Masses

The surgical availability of the mediastinum has stimulated interest in lesions of this area, but a review of the literature leads to confusion more than to clarity. The boundaries of the mediastinum vary from those stated by Maier, 1 who does not include neurogenic tumors because they are in the costovertebral gutter, and not the true mediastinum, through Peabody and others, 2 who include the middle mediastinum in the anterior portion and divide the mediastinum into superior and inferior compartments, each with an anterior and a posterior portion. The boundaries accepted by most authors will be used in this article and be delineated later. Blades, 3 Harrington, 4 and Laipply 5 reviewed this subject, and their combined statistics show that 75% of the anterior mediastinal tumors are of teratoid origin, 52% of the tumors of the middle mediastinum are bronchogenic cysts, 90% of all posterior mediastinal tumors are neuroblastomas, and