Perfusion computed tomography of the liver

Background: Perfusion CT (P-CT) is a relatively new imaging technique that permits the visual and quantitative assessment of the micro- and macrocirculation of a target organ and focal lesions. P-CT has shown promising results in the evaluation of hyper-vascular tumors such as hepatocellular carcinoma (HCC). HCC is the sixth most common cancer globally and it has a poor prognosis when discovered at a late tumor stage. Any improvement in HCC detection would be directly beneficial for patient care. This thesis aims to investigate the strengths and limitations of whole liver P-CT and to evaluate if PCT can improve the detection of hyper-vascular liver lesions in patients with chronic liver disease. Methods: Study I: Twenty-four patients, who underwent dynamic P-CT for detection of HCC were retrospectively divided into three groups: (1) without portal-venous hypertension (PVH) (n = 8), (2) with PVH (n = 8), (3) with PVH and thrombosis (n = 8). Time to peak splenic- and peak renal enhancement (PSE resp. PRE), as well as arterial liver perfusion (ALP), portal- venous liver perfusion (PLP) and hepatic perfusion-index (HPI) of the liver and HCC derived from PSE- versus PRE- based modelling were compared between the groups. Study II: Group A (n=15) and Group B (n= 38) underwent P-CT using 50 ml contrast medium (CM). Group B underwent an additional standard multiphasic liver CT using 120ml (70-143 ml). Triple-arterial CT image sets were reconstructed from P-CT by fusing three dedicated arterial time points. Triple-arterial CT and single-arterial CT were compared by two readers (R1, R2), who assessed subjective image quality (IQ) and HCC detection rate. A third reader assessed objective IQ.Study III: Fifty study participants (Group A) were scanned with P-CT, a high CM volume protocol and bolus-tracking technique to depict ten arterial phases. Time attenuation curves were created for hyper-vascular liver lesions, liver parenchyma and hepatic vascular structures. 16 participants of Group A with lesions were further analyzed and radiation dose-neutral quadruple arterial phase image sets were created (Group A1). Group A1 was then compared to a Control Group (Group B) consisting of 16 consecutive patients undergoing standard single arterial phase scans. Lesion depiction and quantitative IQ were compared. Results: Study I: Time to PSE was significantly delayed in PVH groups 2 and 3 (P = 0.02), whereas PRE was similar in groups 1, 2 and 3 (P > 0.05). In group 1, liver and HCC perfusion parameters were similar for PSE- and PRE-based modelling (all P > 0.05), while significant differences were seen for PLP and HPI (liver only) in group 2 and ALP in group 3 (all P < 0.05). Study II: The mean CTDIvol of triple-arterial CT and single-arterial CT was equivalent (P=0.73). Triple-arterial CT showed lower image noise and better contrast-to-noise-ratio (P<0.001, P=0.032, respectively), but no significant difference in lesion-to-liver-contrast-ratio (P=0.31). Subjective IQ was good for both protocols. The detection rate of the 65 HCC lesions was 82%/83% (R1/R2) at triple-arterial CT and 80%/77% (R1/R2) at single-arterial CT (P=0.4). Study III: Both Group A1 and B had 33 hyper-enhancing liver lesions each. The mean CTDIvol of quadruple-arterial CT and single-arterial CT was equivalent (P=0.16). The mean time to reach peak lesion-to-liver contrast (LLC) was 20.1s (±4.2s) with a range of 12.5s to 29.1s. Quadruple arterial CT performed significantly better than the Control Group in regards to LLC (P= .009), CNR (P= .002), Image Noise (P<0.001) and hepatic artery enhancement(P<0.001). Conclusions: Study I: PSE is significantly delayed in patients with portal venous hypertension, which results in a miscalculation of P-CT parameters. Maximum-slope based P-CT could be improved by replacing the spleen with the kidney as the reference organ. The difference between time to PSE and time to PRE might serve as a non-invasive biomarker of portal venous hypertension. Study II: Radiation dose-equivalent triple arterial phase imaging is feasible and showed superior image quality and similar HCC detection rate as standard single arterial phase CT despite a substantially smaller CM volume. Study III: The optimal scan delay at single arterial phase CT for depiction of hyper-vascular liver lesions occurs at 20 s, when using a high iodine dose CM protocol and bolus-tracking. Fused quadruple arterial phase CT significantly increases lesion depiction, quantitative IQ and hepatic artery enhancement as compared to standard single arterial phase CT, without elevating the total radiation dose

25 Hz adaptation: Influence on recovery time in glaucoma

INTRODUCTION. Normal temporal contrast sensitivity is maximally influenced by pre-adaptation with 25-Hz temporal contrast flicker. The aim of this study was to investigate the effects of 25-Hz contrast adaptation on recovery of contrast sensitivity in normals, patients with ocular hypertension, preperimetric, perimetric and advanced perimetric open-angle glaucoma. MATERIALS AND METHODS. Temporal contrast sensitivity was examined after pre-adaptation with 25 Hz in the following: 43 normals, 14 ocular hypertension, 10 preperimetric primary open-angle glaucoma, and 33 perimetric open-an­gle glaucoma patients. After pre-adaptation (the time after which a test stimulus could be detected again), recovery time (RT) was measured at 3% and 5% test contrast. Additionally, 25 patients with advanced perimetric open-angle glaucoma were measured at 12%, 25%, and 35% contrast and compared to a normal group consisting of 15 subjects. RESULTS. 1. Measurements of RT are reliable (Cronbach’s a &gt; 0.8). 2. RT was age-dependent requiring an age-correction in further analyses. 3. RT3% and RT5% were significantly prolonged in perimetric primary open-angle glau­coma compared to normals (3% test contrast: p = 0.007; 5% test contrast: p = 0.035). 4. Within each group, RT3% and RT5% were significantly different at both test contrasts (normals, perimetric open-angle glaucoma: p &lt; 0.001; ocular hypertension: p = 0.007; preperimetric open-angle glaucoma: p = 0.035). 5. RT3% and RT5% were significantly correlated with mean defect (p &lt; 0.001) and retinal nerve fibre layer thickness (p = 0.018). RT5% was correlated with loss variance (p = 0.048). 6. RT12%, RT25% and RT35% were significantly prolonged in advanced perimetric glaucoma (p &lt; 0.001), and correlated with mean defect (p &lt; 0.001, p = 0.002, p = 0.013) and retinal nerve fibre layer thickness (p &lt; 0.001, p = 0.003, p = 0.013). RT12% was also correlated with loss variance (p = 0.016). CONCLUSIONS. Measurements of RT after 25-Hz pre-adaptation can be used in glaucoma diagnosis and follow-up examination, especially in monitoring glaucoma progress in advanced perimetric primary open-angle glaucoma

Temporal contrast sensitivity: A potential parameter for glaucoma progression, especially in advanced stages

INTRODUCTION. Previously it could be shown that temporal contrast sensitivity is affected by glaucoma and maximally influenced after 25-Hz adaptation in normals. This study investigated different kinds of 25-Hz temporal contrast adaptation on TCS in patients with ocular hypertension, preperimetric primary open-angle glaucoma, and perimetric open-angle glaucoma. Additionally, correlations of measured data with parameters of glaucoma diagnostic were done and assessed for the potential use of TCS as a parameter for glaucoma progression. MATERIALS AND METHODS. One hundred and four subjects were included: 44 normals, 14 ocular hypertensions, 11 preperimetric primary open-angle glaucomas, and 35 perimetric open-angle glaucomas. Using the Erlangen Flicker Test, temporal contrast sensitivity was measured without adaptation, after pre-adaptation and after pre- and re-adaptations at 25 Hz. Reliability analyses were done. RESULTS. All test strategies showed high reliability (a-Cronbach’s &gt; 0.86). In normals, age-dependency of temporal contrast sensitivity without adaptation (p = 0.052) and after pre- and re-adaptation (p = 0.008) was observed. Temporal contrast sensitivity is significantly reduced after pre-adaptation for all subjects (p &lt; 0.001). Reduction of temporal contrast sensitivity after pre- and re-adaptations was significant in all groups (p &lt; 0.001), but it was smaller than after single pre-adaptation (p &lt; 0.001). Temporal contrast sensitivity without adaptation was significantly reduced in patients with perimetric glaucoma (p = 0.040) but not in patients with ocular hypertension and preperimetric glaucoma. Correlation analyses yielded a significant correlation between temporal contrast sensitivity without adaptation and mean defect (p = 0.003, r = –0.329), loss variance (p = 0.027, r = –0.256), and retinal nerve fibre layer thickness (p &lt; 0.001, r = 0.413) for all subjects and between temporal contrast sensitivity after pre-adaptation and mean defect (p = 0.045, r = –0.239). CONCLUSIONS. Temporal contrast sensitivity seems to be affected in perimetric glaucoma with an overall reduction after adaptation. Significant correlations of temporal contrast sensitivity with perimetric and morphologic parameters offer new aspects of its potential use as a glaucoma progressions marker, especially in advanced stages when perimetric diagnosis is limited

The Lid Domain of Caenorhabditis elegans Hsc70 Influences ATP Turnover, Cofactor Binding and Protein Folding Activity

Hsc70 is a conserved ATP-dependent molecular chaperone, which utilizes the energy of ATP hydrolysis to alter the folding state of its client proteins. In contrast to the Hsc70 systems of bacteria, yeast and humans, the Hsc70 system of C. elegans (CeHsc70) has not been studied to date

Calbindin D28k-Immunoreactivity in Human Enteric Neurons

Calbindin (CALB) is well established as immunohistochemical marker for intrinsic primary afferent neurons in the guinea pig gut. Its expression by numerous human enteric neurons has been demonstrated but little is known about particular types of neurons immunoreactive for CALB. Here we investigated small and large intestinal wholemount sets of 26 tumor patients in order to evaluate (1) the proportion of CALB+ neurons in the total neuron population, (2) the colocalization of CALB with calretinin (CALR), somatostatin (SOM) and vasoactive intestinal peptide (VIP) and (3) the morphology of CALB+ neurons. CALB+ neurons represented a minority of myenteric neurons (small intestine: 31%; large intestine: 25%) and the majority of submucosal neurons (between 72 and 95%). In the submucosa, most CALB+ neurons co-stained for CALR and VIP (between 69 and 80%) or for SOM (between 20 and 3%). In the myenteric plexus, 85% of CALB+ neurons did not co-stain with the other markers investigated. An unequivocal correlation between CALB reactivity and neuronal morphology was found for myenteric type III neurons in the small intestine: uniaxonal neurons with long, slender and branched dendrites were generally positive for CALB. Since also other neurons displayed occasional CALB reactivity, this protein is not suited as an exclusive marker for type III neurons

Renal versus splenic maximum slope based perfusion CT modelling in patients with portal-hypertension

PURPOSE To assess liver perfusion-CT (P-CT) parameters derived from peak-splenic (PSE) versus peak-renal enhancement (PRE) maximum slope-based modelling in different levels of portal-venous hypertension (PVH). MATERIAL AND METHODS Twenty-four patients (16 men; mean age 68 ± 10 years) who underwent dynamic P-CT for detection of hepatocellular carcinoma (HCC) were retrospectively divided into three groups: (1) without PVH (n = 8), (2) with PVH (n = 8), (3) with PVH and thrombosis (n = 8). Time to PSE and PRE and arterial liver perfusion (ALP), portal-venous liver perfusion (PLP) and hepatic perfusion-index (HPI) of the liver and HCC derived from PSE- versus PRE-based modelling were compared between the groups. RESULTS Time to PSE was significantly longer in PVH groups 2 and 3 (P = 0.02), whereas PRE was similar in groups 1, 2 and 3 (P > 0.05). In group 1, liver and HCC perfusion parameters were similar for PSE- and PRE-based modelling (all P > 0.05), whereas significant differences were seen for PLP and HPI (liver only) in group 2 and ALP in group 3 (all P < 0.05). CONCLUSION PSE is delayed in patients with PVH, resulting in a miscalculation of PSE-based P-CT parameters. Maximum slope-based P-CT might be improved by replacing PSE with PRE-modelling, whereas the difference between PSE and PRE might serve as a non-invasive biomarker of PVH. KEY POINTS • Peak-splenic enhancement is decreased and delayed in patients with portal-venous hypertension • The maximum-slope method uses PSE to calculate arterial and portal-venous liver perfusion • Peak-renal enhancement (PRE) is insensitive to PVH and might improve perfusion modelling • The difference between PSE and PRE might serve as a non-invasive PVH biomarker

Cardiovascular and Lung Involvement in Patients with Autoimmune Pancreatitis

Introduction: Immunoglobulin G4-related disease (IgG4-RD) is a systemic immune-mediated disease characterised pathologically by the infiltration of IgG4-bearing plasma cells into the involved organs. Autoimmune pancreatitis (AIP) is a form of chronic pancreatitis with a heavy lymphocytic infiltration and two distinct histopathological subtypes, namely: lymphoplasmacytic sclerosing pancreatitis (AIP type 1) and idiopathic duct-centric pancreatitis (AIP type 2). Lung involvement and aortic involvement have been reported in 12% and 9% of patients with systemic IgG4-RD, respectively. In series including patients with AIP, both lung and aortic involvement were described in 2% of the patients. Most of the epidemiological data come from Japan, and there is a lack of information from Europe, especially the Scandinavian countries. Patients and methods: We performed a single-centre retrospective study on a prospectively collected cohort of patients diagnosed with AIP at the Department for Digestive Diseases at Karolinska University Hospital in Stockholm, Sweden, from 2004 to 2019. Demographic and clinical data were collected from the medical charts. Results: One hundred and thirty-three patients with AIP were analysed. Six patients were excluded because they lacked some of the clinical data relevant to the study. Demographic and clinical features of 127 patients were presented. There were 98 patients with AIP type 1-35 (35.7%) female and 63 (64.3%) male, with a mean age of 55.4 ± 18.2. Among them, 15 (15.3%) patients had lung and/or cardiovascular involvement-11 (11.2%) patients had lung involvement, 10 (10.2%) patients had cardiovascular involvement (six patients had both). Most of them (67.0%) had never smoked. The mean follow-up time of the patients with AIP type 1 was 49 months. Conclusions: Lung and/or cardiovascular involvement were diagnosed in 15 (15.3%) patients in our historical cohort of patients with AIP type 1. Most of the lung involvement was presented in the form of nodular lesions in the lungs, non-specific infiltrates, “ground-glass” appearance with pleura thickening, and effusion. Aortic involvement was a major form of vascular involvement in patients with AIP, as in previous published studies on patients with IgG4-RD

Triple Arterial Phase CT of the Liver with Radiation Dose Equivalent to That of Single Arterial Phase CT: Initial Experience

Purpose To develop and evaluate a triple arterial phase CT liver protocol with a similar radiation dose to that of standard single arterial phase CT in study subjects suspected of having hepatocellular carcinoma (HCC). Materials and Methods The study consisted of a retrospective part A for protocol development (n = 15) and a prospective part B to evaluate diagnostic accuracy (n = 38). All 53 participants underwent perfusion CT with 50 mL contrast material between August 2013 and September 2014. Group B underwent an additional standard multiphasic liver CT examination with 120 mL of contrast material (range, 70-143 mL). Image sets from triple arterial phase imaging were reconstructed from perfusion CT by fusing images from three dedicated arterial time points. Triple arterial phase CT and standard single arterial phase CT were compared by two readers, who assessed subjective image quality and HCC detection rate. A third reader served as reference reader and assessed objective image quality. The paired Student t test, Wilcoxon signed rank test, jackknife alternative free-response receiver operating characteristic (JAFROC), and JAFROC curve were applied. Results The mean volume CT dose index was 11.6 mGy for triple arterial phase CT and 11.9 mGy for standard single arterial phase CT (P = .73). Triple arterial phase CT showed lower image noise and better contrast-to-noise ratio compared with standard single arterial phase CT (P < .001 and P = .032, respectively); however, there was no significant difference in lesion-to-liver-contrast ratio (P = .31). Subjective image quality was good for both protocols. The detection rate of the 65 HCC lesions was 82% for reader 1 and 83% for reader 2 at triple arterial phase CT and 80% for reader 1 and 77% for reader 2 at standard single arterial phase CT (P = .4). Conclusion Triple arterial phase imaging is feasible at the same radiation dose as that used for standard single arterial phase CT. Triple arterial phase imaging provides equivalent to superior image quality and equal HCC detection rate despite the use of less than half the contrast material dose used at standard single arterial phase CT. © RSNA, 2018