Diagnosis: What Is the Structure of Its Reasoning?

How does the diagnosis process work? This essay traces the philosophical underpinnings of diagnosis from Hume through Kant, Peirce, and Popper, analyzing how pathologists amalgamate sensibility, intuition, and imagination to form new hypotheses that can be tested by evidence and experience.

Transcriptome and Secretome Analysis of Intra-Mammalian Life-Stages of Calicophoron daubneyi Reveals Adaptation to a Unique Host Environment.

Paramphistomosis, caused by the rumen fluke, Calicophoron daubneyi, is a parasitic infection of ruminant livestock, which has seen a rapid rise in prevalence throughout Western Europe in recent years. After ingestion of metacercariae (parasite cysts) by the mammalian host, newly excysted juveniles (NEJs) emerge and invade the duodenal submucosa, which causes significant pathology in heavy infections. The immature flukes then migrate upward, along the gastrointestinal tract, and enter the rumen where they mature and begin to produce eggs. Despite their emergence, and sporadic outbreaks of acute disease, we know little about the molecular mechanisms used by C. daubneyi to establish infection, acquire nutrients, and avoid the host immune response. Here, transcriptome analysis of four intramammalian life-cycle stages, integrated with secretome analysis of the NEJ and adult parasites (responsible for acute and chronic diseases, respectively), revealed how the expression and secretion of selected families of virulence factors and immunomodulators are regulated in accordance with fluke development and migration. Our data show that while a family of cathepsins B with varying S2 subsite residues (indicating distinct substrate specificities) is differentially secreted by NEJs and adult flukes, cathepsins L and F are secreted in low abundance by NEJs only. We found that C. daubneyi has an expanded family of aspartic peptidases, which is upregulated in adult worms, although they are under-represented in the secretome. The most abundant proteins in adult fluke secretions were helminth defense molecules that likely establish an immune environment permissive to fluke survival and/or neutralize pathogen-associated molecular patterns such as bacterial lipopolysaccharide in the microbiome-rich rumen. The distinct collection of molecules secreted by C. daubneyi allowed the development of the first coproantigen-based ELISA for paramphistomosis which, importantly, did not recognize antigens from other helminths commonly found as coinfections with rumen fluke.

Fasciola hepatica Gastrodermal Cells Selectively Release Extracellular Vesicles via a Novel Atypical Secretory Mechanism.

The liver fluke, Fasciola hepatica, is an obligate blood-feeder, and the gastrodermal cells of the parasite form the interface with the host's blood. Despite their importance in the host-parasite interaction, in-depth proteomic analysis of the gastrodermal cells is lacking. Here, we used laser microdissection of F. hepatica tissue sections to generate unique and biologically exclusive tissue fractions of the gastrodermal cells and tegument for analysis by mass spectrometry. A total of 226 gastrodermal cell proteins were identified, with proteases that degrade haemoglobin being the most abundant. Other detected proteins included those such as proton pumps and anticoagulants which maintain a microenvironment that facilitates digestion. By comparing the gastrodermal cell proteome and the 102 proteins identified in the laser microdissected tegument with previously published tegument proteomic datasets, we showed that one-quarter of proteins (removed by freeze-thaw extraction) or one-third of proteins (removed by detergent extraction) previously identified as tegumental were instead derived from the gastrodermal cells. Comparative analysis of the laser microdissected gastrodermal cells, tegument, and F. hepatica secretome revealed that the gastrodermal cells are the principal source of secreted proteins, as well as showed that both the gastrodermal cells and the tegument are likely to release subpopulations of extracellular vesicles (EVs). Microscopical examination of the gut caeca from flukes fixed immediately after their removal from the host bile ducts showed that selected gastrodermal cells underwent a progressive thinning of the apical plasma membrane which ruptured to release secretory vesicles en masse into the gut lumen. Our findings suggest that gut-derived EVs are released via a novel atypical secretory route and highlight the importance of the gastrodermal cells in nutrient acquisition and possible immunomodulation by the parasite.

Seasonal variation of Fasciola hepatica antibodies in dairy herds in Northern Ireland measured by bulk tank milk ELISA.

Bovine fasciolosis, caused by the infection of the trematode parasite Fasciola hepatica, remains a problem in dairy herds causing significant production losses. In this study, bulk milk tank samples were utilised to generate a comprehensive survey of the variation in liver fluke exposure over the four seasons of 2016 in Northern Ireland (NI). Samples were tested using an antibody ELISA test; within-herd prevalence levels were categorised relative to sample-to-positive ratio (S/P%). Overall, 1494 herds (~ 50% of all active dairy farms in NI) were sampled. In total, 5750 samples were tested with 91% of herds having a sample result for each season. The proportion of herds with evidence of liver fluke exposure was very high across the year, with 93.03% of all bulk milk samples having some indication of liver fluke antibody presence. A high proportion of samples (2187/5750; 38.03%) fell within the highest infection class (indicating high within-herd prevalence). There was significant seasonal variation in the mean S/P%. A multivariable random effect ordinal logit model suggested that the greatest probability of being in a higher infection class was in winter, whilst the lowest was recorded during summer. There was a significant negative association between increasing herd liver fluke infection class and herd size. Furthermore, there was significant variation in infection levels across regions of Northern Ireland, with higher infection levels in northern administrative areas. This study demonstrates the very high liver fluke exposure in this region of Europe, and that risk is not equally distributed spatially or across seasons in dairy herds.

Control of Nematodirus spp. infection by sheep flock owners in Northern Ireland.

BACKGROUND: To address a lack of information on the control of ovine helminth parasites in Northern Ireland (NI), a number of research projects have been undertaken, dealing with gastrointestinal nematodes, tapeworms and liver fluke. This investigation concerns Nematodirus and concentrates on three aspects of disease: farm management strategies for its control, derived from the results of a Questionnaire; the efficacy of treatment used by farmers, as determined by a coprological survey; and the hatching requirements of Nematodirus eggs, that is, whether prolonged chilling is a pre-requisite for hatching. RESULTS: A Questionnaire was sent to 252 sheep farmers in NI in March 2012 (covering the years 2009-2012) and replies were received from 228 farmers. Under-dosing, inaccurate calibration of equipment and inappropriate product choice were poor practices identified. Following this survey, the efficacy of treatment of Nematodirus spp. in sheep flocks was evaluated in April and May 2012. Sampling kits were sent to 51 flock owners, all of whom returned pre- and post-anthelmintic dosing faecal samples to the laboratory for analysis. At the time of treatment, 41 flocks were positive for Nematodirus (as diagnosed by the presence of eggs). Reduced benzimidazole efficacy was detected in 35.7% of flocks tested (n = 28). Although only involving a small number of flocks, reduced efficacy of levamisole treatment was detected in 50%, of avermectins in 33% and of moxidectin in 75% of flocks tested (n = 2, 6 and 4, respectively). In the egg hatch experiment, carried out under "chilled" and "non-chilled" conditions, 43% of the eggs in the "non-chilled" group were able to hatch, compared to 100% in the "chilled" group. CONCLUSIONS: The identification of inefficient control strategies argues for continued education of stockholders, in order to improve their management programmes. This is particularly important where the practices might impact on the development of anthelmintic resistance, which has been shown to exist on NI farms. The appropriate choice of anthelmintic is a vital part of this plan. The ability of eggs to hatch under non-chilled conditions demonstrates a flexibility in hatching behaviour. This may represent an adaptation to climate change and account for the recent emergence of a second, autumnal peak of infection.

Sagittal alignment after lumbar interbody fusion: comparing anterior, lateral, and transforaminal approaches.

STUDY DESIGN: Retrospective radiographic analysis. OBJECTIVE: To determine which lumbar interbody technique is most effective for restoring lordosis, increasing disk height, and reducing spondylolisthesis. SUMMARY OF BACKGROUND DATA: Lumbar interbody fusions are performed in hopes of increasing fusion potential, correcting deformity, and indirectly decompressing nerve roots. No published study has directly compared anterior, lateral, and transforaminal lumber interbody fusions in terms of ability to restore lordosis, increase disk height, and reduce spondylolisthesis. MATERIALS AND METHODS: Lumbar interbody fusion techniques were retrospectively compared in terms of improvement of lordosis, disk height, and spondylolisthesis between preoperative and follow-up lateral radiographs. RESULTS: A total of 220 consecutive patients with 309 operative levels were compared by surgery type: anterior (184 levels), lateral (86 levels), and transforaminal (39 levels). Average follow-up was 19.2 months (range, 1-56 mo), with no statistical difference between the groups. Intragroup analysis showed that the anterior (4.5 degrees) and lateral (2.2 degrees) groups significantly improved lordosis from preoperative to follow-up, whereas the transforaminal (0.8 degrees) group did not. Intergroup analysis showed that the anterior group significantly improved lordosis more than both the lateral and transforaminal groups. The anterior (2.2 mm) and lateral (2.0 mm) groups both significantly improved disk height more than the transforaminal (0.5 mm) group. All 3 groups significantly reduced spondylolisthesis, with no difference between the groups. CONCLUSIONS: After lumbar interbody fusion, improvement of lordosis was significant for both the anterior and lateral groups, but not the transforaminal group. Intergroup analysis showed the anterior group had significantly improved lordosis compared to both the other groups. The anterior and lateral groups had significantly increased disk height compared to the transforaminal group. All the 3 groups significantly reduced spondylolisthesis, with no difference between the groups.

A Novel Prototype Biosensor Array Electrode System for Detecting the Bacterial Pathogen Salmonella typhimurium.

Salmonellosis caused by Salmonella sp. has long been reported all over the world. Despite the availability of various diagnostic methods, easy and effective detection systems are still required. This report describes a dialysis membrane electrode interface disc with immobilized specific antibodies to capture antigenic Salmonella cells. The interaction of a specific Salmonella antigen with a mouse anti-Salmonella monoclonal antibody complexed to rabbit anti-mouse secondary antibody conjugated with HRP and the substrate o-aminophenol resulted in a response signal output current measured using two electrode systems (cadmium reference electrode and glassy carbon working electrode) and an agilent HP34401A 6.5 digital multimeter without a potentiostat or applied potential input. A maximum response signal output current was recorded for various concentrations of Salmonella viz., 3, 30, 300, 3000, 30,000 and 300,000 cells. The biosensor has a detection limit of three cells, which is very sensitive when compared with other detection sensors. Little non-specific response was observed using Streptococcus, Vibrio, and Pseudomonas sp. The maximum response signal output current for a dialysis membrane electrode interface disc was greater than that for gelatin, collagen, and agarose. The device and technique have a range of biological applications. This novel detection system has great potential for future development and application in surveillance for microbial pathogens.

Rabbit Haemorrhagic Disease Virus 2 (RHDV2; GI.2) in Ireland Focusing on Wild Irish Hares (Lepus timidus hibernicus): An Overview of the First Outbreaks and Contextual Review.

Rabbit haemorrhagic disease virus 2 (RHDV2; GI.2) is a pathogenic lagovirus that emerged in 2010, and which now has a global distribution. Outbreaks have been associated with local population declines in several lagomorph species, due to rabbit haemorrhagic disease (RHD)-associated mortality raising concerns for its potential negative impact on threatened or vulnerable wild populations. The Irish hare (Lepus timidus hibernicus) is endemic to Ireland, and is of conservation interest. The first cases of RHDV2 in Ireland were reported in domestic rabbits (Oryctolagus cuniculus) in 2016, soon followed by the first known case in a wild rabbit also in 2016, from a population reported to be experiencing high fatalities. During summer 2019, outbreaks in wild rabbits were confirmed in several locations throughout Ireland. Six cases of RHDV2 in wild hares were confirmed between July and November 2019, at four locations. Overall, 27 cases in wildlife were confirmed in 2019 on the island of Ireland, with a predominantly southern distribution. Passive surveillance suggests that the Irish hare is susceptible to lethal RHDV2 infection, and that spillover infection to hares is geographically widespread in eastern areas of Ireland at least, but there is a paucity of data on epidemiology and population impacts. A literature review on RHD impact in closely related Lepus species suggests that intraspecific transmission, spillover transmission, and variable mortality occur in hares, but there is variability in reported resistance to severe disease and mortality amongst species. Several key questions on the impact of the pathogen in Irish hares remain. Surveillance activities throughout the island of Ireland will be important in understanding the spread of infection in this novel host.

The effect of naturally acquired rumen fluke infection on animal health and production in dairy and beef cattle in the UK.

The incidence of paramphistomosis, caused by the rumen fluke, Calicophoron daubneyi, has greatly increased within Europe in the last 15-20 years. However, the production impacts of this disease are poorly understood. This study firstly aimed to investigate the prevalence of rumen fluke in England and Northern Ireland (NI) by conducting an abattoir survey of dairy and beef cattle which also allowed the impact of rumen fluke on carcass weight, conformation and fat classification to be assessed. Secondly, an experiment aimed to assess the impact of C. daubneyi infection on diarrhea score, production loss and welfare in dairy heifers, while also evaluating the impacts of treating infected heifers with oxyclozanide. Rumen fluke prevalence was greater in NI than in England, with 53.8% (95% CI 51.9 - 55.9%) of the NI cattle carcases sampled being infected compared to 16.3% (95% CI 15.8 - 16.8%) and 17.9% (95% CI 17.4 - 18.4%) detected at the two abattoirs in England. However, there was no significant difference (P > 0.05) in the cold carcass weight between infected and non-infected cattle. Similarly, carcass conformation and fat classification were unaffected (P > 0.05) by the presence of rumen fluke. In the second experiment, daily live weight gain (DLWG), diarrhea score and welfare score were also unaffected (P > 0.05) by rumen fluke infection and by oxyclozanide treatment against rumen fluke. The farms in this experiment were managed to a high standard and animals had no intercurrent disease. Therefore, these findings suggest that on well-managed farms, production losses (growth rates) should not be compromised as a result of sub-clinical rumen fluke infection.

Case Report of Puffinosis in a Manx Shearwater (Puffinus puffinus) Suggesting Environmental Aetiology.

Puffinosis is a disease of a range of seabirds characterised by dorsal and ventral blistering of their webbed feet, conjunctivitis, dry necrosis, leg spasticity, head shaking, loss of balance, tremors, and death. It is associated with Manx shearwaters (Puffinus puffinus), frequently affecting chicks within their underground nesting burrows. The aetiology of the disease is unclear but has been attributed to a type-2 coronavirus associated with Neotombicula mites as a potential vector. However, there is some uncertainty given potential laboratory contamination with mouse hepatitis virus and failure to fulfil Koch's postulates, with birds injected with isolates remaining healthy. We describe a detailed case report of puffinosis in a Manx Shearwater covering necropsy, histology, bacteriology, and metagenomics including viral sequencing. We found no evidence of viral infection or parasites. Our results are consistent with an entirely environmental aetiology, with caustic faecal ammonia in damp nesting burrows causing conjunctivitis and foot dermatitis breaking the skin, allowing common soil bacteria (i.e., Flavobacterium, Staphylococcus and Serratia spp., Clostridia perfringens and Enterococcus faecalis) to cause opportunistic infection, debilitating the bird and leading to death. A similar condition (foot pad dermatitis or FPD) has been reported in broiler chickens, attributed to caustic faeces, high humidity, and poor environmental conditions during indoor rearing, preventable by adequate ventilation and husbandry. This is consistent with puffinosis being observed in Shearwater nesting burrows situated in tall, dense, vegetation (e.g., bracken Pteridium aquilinum) but rarely reported in burrows situated in well-ventilated, short coastal grasslands. This proposed environmental aetiology accounts for the disease's non-epizootic prevalence, spatial variation within colonies, and higher frequency in chicks that are restricted to nesting burrows.

Fasciola hepatica: time-dependent disruption of spermatogenesis following in vivo treatment with triclabendazole.

Sheep infected with the Cullompton isolate of Fasciola hepatica were treated with triclabendazole at a concentration of 10 mg/kg at 12 weeks post-infection. Adult flukes were recovered from the liver and, where present, from the gall bladder at 48, 72 and 96 h post-treatment (pt). Gross changes to the spermatogenic cells of the testis were examined by histology and ultrastructural alterations were visualised via transmission electron microscopy. Disruption was progressive in nature, with the testis tubules becoming shrunken, vacuolated and gradually more denuded of cellular content over the 96-h time period. From 48 h pt, the number of primary and secondary spermatogonia decreased and multinucleate spermatogonial cells were frequent. Later, developmental stages were uncommon, giving rise to much empty space within the tubules. By 72 h pt, the tubules contained many apoptotic and degraded cells and had an extremely disorganised appearance. At 96 h pt, the tubules were almost completely empty, with the exception of the remains of degraded spermatogenic cells. These results indicate that triclabendazole severely disrupts spermatogenesis in the liver fluke from 48 h pt in vivo.

Philosophical foundations for digital ethics and AI Ethics: a dignitarian approach.

AI Ethics is a burgeoning and relatively new field that has emerged in response to growing concerns about the impact of artificial intelligence (AI) on human individuals and their social institutions. In turn, AI ethics is a part of the broader field of digital ethics, which addresses similar concerns generated by the development and deployment of new digital technologies. Here, we tackle the important worry that digital ethics in general, and AI ethics in particular, lack adequate philosophical foundations. In direct response to that worry, we formulate and rationally justify some basic concepts and principles for digital ethics/AI ethics, all drawn from a broadly Kantian theory of human dignity. Our argument, which is designed to be relatively compact and easily accessible, is presented in ten distinct steps: (1) what "digital ethics" and "AI ethics" mean, (2) refuting the dignity-skeptic, (3) the metaphysics of human dignity, (4) human happiness or flourishing, true human needs, and human dignity, (5) our moral obligations with respect to all human real persons, (6) what a natural automaton or natural machine is, (7) why human real persons are not natural automata/natural machines: because consciousness is a form of life, (8) our moral obligations with respect to the design and use of artificial automata or artificial machines, aka computers, and digital technology more generally, (9) what privacy is, why invasions of digital privacy are morally impermissible, whereas consensual entrances into digital privacy are either morally permissible or even obligatory, and finally (10) dignitarian morality versus legality, and digital ethics/AI ethics. We conclude by asserting our strongly-held belief that a well-founded and generally-accepted dignitarian digital ethics/AI ethics is of global existential importance for humanity.

Bio-Fabrication of Human Amniotic Membrane Zinc Oxide Nanoparticles and the Wet/Dry HAM Dressing Membrane for Wound Healing.

The preparation of unique wet and dry wound dressing products derived from unprocessed human amniotic membrane (UP-HAM) is described. The UP-HAM was decellularized, and the constituent proteins were cross-linked and stabilized before being trimmed and packed in sterile Nucril-coated laminated aluminium foil pouches with isopropyl alcohol to manufacture processed wet human amniotic membrane (PW-HAM). The dry type of PD-HAM was prepared by decellularizing the membrane, UV irradiating it, lyophilizing/freeze-drying it, sterilizing it, and storing it at room temperature. The UP-HAM consists of a translucent yellowish mass of flexible membranes with an average thickness of 42 µm. PW-HAM wound dressings that had been processed, decellularized, and dehydrated had a thinner average thickness of 30 µm and lacked nuclear-cellular structures. Following successful decellularization, discrete bundle of fibrous components in the stromal spongy layers, microvilli and reticular ridges were still evident on the surface of the processed HAM, possibly representing the location of the cells that had been removed by the decellularization process. Both wet and dry HAM wound dressings are durable, portable, have a shelf life of 3-5 years, and are available all year. A slice of HAM dressing costs 1.0 US$/cm2. Automation and large-scale HAM membrane preparation, as well as storage and transportation of the dressings, can all help to establish advanced technologies, improve the efficiency of membrane production, and reduce costs. Successful treatment of wounds to the cornea of the eye was achieved with the application of the HAM wound dressings. The HAM protein analysis revealed 360 µg proteins per gram of tissue, divided into three main fractions with MWs of 100 kDa, 70 kDa, and 14 kDa, as well as seven minor proteins, with the 14 kDa protein displaying antibacterial properties against human pathogenic bacteria. A wide range of antibacterial activity was observed after treatment with 75 µg/ml zinc oxide nanoparticles derived from human amniotic membrane proteins (HAMP-ZnO NP), including dose-dependent biofilm inhibition and inhibition of Gram-positive (S. aureus, S. mutans, E. faecalis, and L. fusiformis) and Gram-negative bacteria (S. sonnei, P. aeruginosa, P. vulgaris, and C. freundii).

Apparent diffusion coefficient of fibrosis and regenerative nodules in the cirrhotic liver at MRI.

OBJECTIVE: The purpose of this article is to compare the apparent diffusion coefficient (ADC) of fibrosis and regenerative nodules in the cirrhotic liver at MRI, both in vivo and ex vivo. SUBJECTS AND METHODS: A prospective ex vivo and in vivo study was performed at a tertiary liver center. To characterize the diffusion properties of cirrhotic liver, 63 human liver specimens obtained anonymously from 23 freshly explanted cirrhotic livers underwent T1-, T2-, and diffusion-weighted MRI ex vivo. ADC values of fibrotic bridges and regenerative nodules were calculated. In vivo conventional and diffusion-weighted MRI was performed for 17 cirrhotic patients (12 men and five women; mean age, 54 years; range, 34-77 years) with focal areas of confluent fibrosis. ADC values of confluent fibrosis and background cirrhotic liver parenchyma were calculated. Log-transformed ADC values of fibrosis and regenerative nodules were compared between ex vivo and in vivo images. RESULTS: Ex vivo, the mean ADC of fibrotic bridges (0.55 +/- 0.24 mm(2)/s [SD]) was greater than that of regenerative nodules (0.36 +/- 0.18 x 10(-3) mm(2)/s) (p < 0.0001). In vivo, the mean ADC value of confluent fibrosis (2.07 +/- 0.39 x 10(-3) mm(2)/s) was greater than that of background cirrhotic liver parenchyma (1.53 +/- 0.35 x 10(-3) mm(2)/s) (p < 0.0001). CONCLUSION: The mean ADC of fibrosis is significantly greater than that of regenerative nodules both in vivo and ex vivo. The prevailing paradigm that fibrosis causes the reduced liver ADC observed in cirrhosis may need modification.

Fasciola hepatica: disruption of spermatogenesis by the fasciolicide compound alpha.

Sheep infected with the triclabendazole-susceptible Cullompton isolate of Fasciola hepatica were dosed with 15 mg/kg of compound alpha at 12 weeks post-infection. Adult flukes were recovered from the bile ducts at 24, 48, and 72 h post-treatment (p.t.). Changes to the spermatogenic cells in the testis were examined by histology and transmission electron microscopy. Disruption to the testes became increasingly severe over time. The testis tubules shrank in size, became vacuolated, and contained fewer cells. Identification of cell types became difficult, and apoptotic eosinophilic bodies were the predominant feature at 72 h p.t. Changes to the spermatogonia were evident at 24 h p.t., the cells containing swollen and electron-lucent mitochondria. The proportion of tertiary spermatogonia increased at 48 h p.t., and they showed signs of autophagy. Multinucleate spermatogonia were a feature of drug treatment at this time point, and they contained autophagic vacuoles. By 72 h p.t., it was difficult to identify primary and secondary spermatogonia, and there were no recognisable clusters of tertiary spermatogonia. Most spermatogonial cells were multinucleate and in the process of breaking down. With regard to the primary spermatocytes, fragmentation of the cytophore was observed at 24 h p.t. Intact rosettes were rare after 48 h treatment; collections of cells were seen, but were not organised into clusters. By 72 h p.t., no spermatocyte cells could be recognised. The results indicate that spermatogenesis was severely affected by compound alpha.

Arthroscopic Repair for Posterior Shoulder Instability: Case series and surgical outcome.

PURPOSE: This study evaluates outcomes of a consistent arthroscopic stabilization technique for recurrent posterior instability. METHODS: 79 shoulders with symptomatic posterior instability treated with arthroscopic repair and evaluated at a follow-up of 36 months. The mean age was 25.4 years of which 66 males and 13 females, and in 75% the dominant shoulder was affected. A known traumatic injury had occurred in 80%, with 25% having a documented dislocation. Arthroscopic repair was performed through an anterosuperior 12 O'clock viewing portal. Suture anchor repairs were performed in 60 cases and plication to the intact labrum in 19. A shoulder immobilizer was used for 4 weeks, followed by progressive range of motion, weightlifting at 3 months and return to contact sports at 6 months. The 79 cases had complete pre-op and post-op shoulder outcome scores. RESULTS: Significant improvement from preoperatively to final follow-up was seen for ASES scores, from 58 to 93. All patients returned to their previous level of athletic activity. Two patients reported postoperative instability; none required reoperation. There were no other postoperative complications. CONCLUSIONS: This study represents a consecutive series of patients with recurrent posterior instability undergoing arthroscopic posterior stabilization. In this population arthroscopic posterior labral repair and capsular plication provided significant clinical improvement with low recurrence and revision rate.

Fatty liver disease: MR imaging techniques for the detection and quantification of liver steatosis.

Fatty liver disease is the most common cause of chronic liver disease in the United States. Noninvasive detection and quantification of fat is becoming more and more important clinically, due in large part to the growing prevalence of nonalcoholic fatty liver disease. Steatosis, the accumulation of fat-containing vacuoles within hepatocytes, is a key histologic feature of fatty liver disease. Liver biopsy, the current standard of reference for the assessment of steatosis, is invasive, has sampling errors, and is not appropriate in some settings. Several magnetic resonance (MR) imaging-based techniques--including chemical shift imaging, frequency-selective imaging, and MR spectroscopy--are currently in clinical use for the detection and quantification of fat-water admixtures, with each technique having important advantages, disadvantages, and limitations. These techniques permit the breakdown of the net MR signal into fat and water signal components, allowing the quantification of fat in liver tissue, and are increasingly being used in the diagnosis, treatment, and follow-up of fatty liver disease.

Double-contrast MRI for accurate staging of hepatocellular carcinoma in patients with cirrhosis.

OBJECTIVE: The aim of this study was to evaluate the accuracy of a double-contrast MRI protocol in staging of hepatocellular carcinoma (HCC) in patients with cirrhosis. MATERIALS AND METHODS: This cross-sectional study was performed at a tertiary liver care center. Forty-eight patients with cirrhosis underwent double-contrast MRI for clinical care and liver transplantation. For each MRI examination, superparamagnetic iron oxide was infused, and 2D T2*-weighted spoiled gradient-recalled echo and T2-weighted echo-train spin-echo MR images were obtained for assessment of phagocytic function. Immediately afterward, a low-molecular-weight gadolinium compound was injected, and 3D T1-weighted spoiled gradient-recalled echo images were acquired dynamically for assessment of vascularity. Two blinded radiologists independently reviewed all MR images and assigned per-lesion and per-patient cancer confidence scores to determine the American Liver Tumor Study Group tumor stage. The imaging-based cancer scores and tumor stages were correlated with pathology reports. Performance parameters were computed for imaging-based measurements. RESULTS: Of the 48 study subjects, 25 had HCC (three, T1; 18, T2; one, T3; one, T4a; two, T4b). In total, there were 37 HCC nodules. The accuracy of MRI in prediction of pathologic tumor stage was 81-85% depending on the radiologist. Per-patient and per-lesion sensitivity in the diagnosis of HCC were 96% and 81% for one radiologist and 96% and 89% for the other. CONCLUSION: A double-contrast MRI protocol has high accuracy in staging of HCC in patients with cirrhosis.

Cirrhosis-associated hepatocellular nodules: correlation of histopathologic and MR imaging features.

Cirrhotic livers are characterized by advanced fibrosis and the formation of hepatocellular nodules, which are classified histologically as either (a) regenerative lesions (eg, regenerative nodules, lobar or segmental hyperplasia, focal nodular hyperplasia) or (b) dysplastic or neoplastic lesions (eg, dysplastic foci and nodules, hepatocellular carcinomas). The differentiation of these lesions is important because regenerative nodules are benign, whereas dysplastic and neoplastic nodules are premalignant and malignant, respectively. However, their accurate characterization may be difficult even at histopathologic analysis. Differential diagnosis may be facilitated by comparing the clinical and pathologic findings with radiologic imaging features; in particular, nodule size, vascularity, hepatocellular function, and Kupffer cell density assessed at magnetic resonance (MR) imaging are suggestive of the correct diagnosis. MR imaging is more useful than computed tomography for such assessments because it provides better soft-tissue contrast and a more nuanced depiction of different tissue properties. Moreover, a wider variety of contrast agents is available for use in MR imaging. Familiarity with the MR imaging characteristics of cirrhosis-associated hepatocellular nodules is therefore important for optimal diagnosis and management of cirrhotic disease.