Sarah Keller

Imaging of appendicitis in adults.

UNLABELLED Three imaging modalities are available for the diagnosis of acute appendicitis: ultrasound (US), computed tomography (CT), and magnetic resonance imaging (MRI). Transabdominal ultrasound should be the first-line imaging test. Abdominal CT is superior to US and is required immediately in patients with atypical clinical presentation of appendicitis and suspected perforation. However, low-dose unenhanced CT is equal to standard-dose CT with intravenous contrast agents in the detection of five signs of acute appendicitis (thickened appendiceal wall more than 2 mm, cross-sectional diameter greater than 6 mm, periappendicitis, abscess, and appendicolith). MRI is necessary in pregnant women and young adults. This review illustrates the principles of state-of-the-art imaging techniques and their clinical relevance. KEY POINTS • US is the basic diagnostic method in case of suspected appendicitis.• CT is necessary in patients with atypical presentation of appendicitis.• MRI should be the first-line imaging test in pregnant women.

Postmortem 31P magnetic resonance spectroscopy of the skeletal muscle: α-ATP/Pi ratio as a forensic tool?

PURPOSE Phosphor magnetic resonance spectroscopy ((31)P MRS) is an established method for metabolic examinations of resting and exercising skeletal muscle. So far, there are few MRS investigations of human corpses. The aim of this study was to investigate the temporal postmortem pattern of phosphor metabolites in the adductor magnus muscle and to check the value of MRS as a forensic tool, especially for the determination of the time of death. MATERIAL AND METHODS Eight corpses, died of natural cause, were examined (5 males, 3 females; age: 73±7 y, weight 65.8±15.9 kg). A control group of 3 subjects (2 males, 1 female, mean age: 51±24 y, range: 24-69 y, mean body weight: 84.0±16.5 kg) was examined at a single time point as well. (31)P MRS was performed on a 1.5 T MRI (TR 700 ms, TE 0.35 ms, averages 256, flip angle 90°). A standard (31)P/(1)H heart/liver coil was employed (receiver coil diameter 12 cm). The (31)P MRS scans were repeated in intervals of 1 h over a period from 4.5 to 24 h postmortem (p.m.). The core temperature was rectally measured throughout the MRI examination. RESULTS The mean core temperature decreased from 36.0°C to 25.7°C. In vivo and ex vivo spectra showed characteristic differences, especially the PCr metabolite was no longer detectable after 10 h p.m. The α-ATP/Pi ratio decreased with time from 0.445 to 0.032 over 24 h p.m. CONCLUSION There is a characteristic postmortem time pattern of the phosphor metabolites. Especially the acquired α-ATP/Pi ratio could be described by a significant exponential time course (r(2)=0.92, p<0.001). (31)P MRS might be added to the postmortem imaging methods.

Association of gadolinium-enhanced magnetic resonance imaging with hepatic fibrosis and inflammation in primary sclerosing cholangitis

Objective To evaluate magnetic resonance imaging (MRI) parameters T2 signal, contrast enhancement (CE), and relative liver enhancement (RLE) of extracellular gadolinium-based contrast agent (GBCA)-enhanced MRI as a marker for hepatic fibrosis and inflammation in patients with primary sclerosing cholangitis (PSC). Methods 3.0-Tesla MRI scans and liver biopsies of 40 patients (41.2 ± 17.1 years) were retrospectively reviewed. Biopsies were obtained within a mean time of 54 ± 55 days to MRI scans and specimens were categorized according to Ishak modified hepatic activity index (mHAI) and Scheuer staging of fibrosis. T2 signal (N = 40), CE alterations (N = 29), and RLE (N = 29) were assessed by two raters. Mixed-effects regression models were applied to estimate the association between histopathology and MRI parameters. Results No significant association was observed between T2 signal or CE alterations with stages of fibrosis or mHAI grading. Regression models revealed significant positive associations of portal venous phase RLE with mHAI grade ≥ 7 points [β = 25.5; 95% CI (2.53; 48.62); p = 0.04] and delayed phase RLE with stages of fibrosis [stage 2: β = 35.13; 95% CI (11.35; 58.87); p = 0.007; stage 3/4: β = 69.24; 95% CI (45.77; 92.75); p < 0.001]. The optimal cut-off value of 66.6% delayed phase RLE distinguished fibrosis stages 0–2 from 3–4 with a sensitivity of 0.833 and specificity of 0.972. Inter-rater reliability (IRR) for quantification of RLE was ‘excellent’ (r = 0.90–0.98). IRR was ‘substantial’ for detection of T2 signal in the right liver lobe (RL) (Kappa = 0.77) and ‘almost perfect’ for T2 signal of the left liver lobe (LL) and CE of both lobes (Kappa = 0.87–1.0). Conclusion The simple and reproducible method of RLE quantification on standard extracellular GBCA-enhanced MRI may provide a correlate measure of advanced stages of hepatic fibrosis and potentially also inflammation in PSC patients, if validated in larger cohorts.

Prevalence of adult Pompe disease in patients with proximal myopathic syndrome and undiagnosed muscle biopsy

We examined patients with limb-girdle muscle weakness and/or hyper-CKaemia and undiagnosed muscle biopsy for late onset Pompe disease (LOPD). Patients with an inconclusive limb-girdle muscle weakness who presented at our neuromuscular centre between 2005 and 2015 with undiagnosed muscle biopsies were examined by dry blood spot testing (DBS) including determination of the enzyme activity of acid alpha-glucosidase (GAA). In the case of depressed enzyme activity, additional gene testing of the GAA gene was carried out. Of the 340 evaluated muscle biopsies, 69 patients fulfilled the inclusion criteria and were examined with DBS. Among those patients, 76% showed a limb-girdle muscle weakness and 14% showed a hyper-CKaemia. A diagnosis of LOPD could be established in the case of two patients (2.9%) with reduced GAA enzyme activity and proof of mutations in the GAA gene. One of the two patients presents in the muscle biopsy suggestive features of Pompe disease including vacuoles with positive acid phosphatase reaction. In summary, our results show that a muscle biopsy can be helpful in identifying LOPD patients, but vacuolation with glycogen storage can also be absent. An inconspicuous muscle biopsy does not rule out Pompe disease. Consequently, all patients with limb-girdle muscle weakness should be examined by DBS before conducting a muscle biopsy.

Diagnosing acute pancreatitis-Clinical and radiological characterisation of patients without threefold increase of serum lipase

OBJECTIVES Diagnosing acute pancreatitis (AP) may be challenging in patients with acute abdominal pain but missing threefold increased serum lipase levels (Lip-). This studyaims both to characterize these patients using clinical, radiological and mortality data, and to assess the group of patients who need contrast-enhanced computed tomography (CECT). METHODS In this retrospective, IRB approved study 234 consecutive patients with AP were investigated. Inclusion criteria were single (SAP) and recurrent attacks (RAP) of AP and CECT ≥72h after onset of symptoms. Severity of AP was assessed by C-reactive protein at 48h after hospital admission and using 3 CT-based scores (CTSI, mCTSI, EPIC) by 2 observers. Mortality rates from pancreatic and non-pancreatic causes were noted with regard to lipase increase. Results were compared with paired t-test and Wilcoxon signed-rank test. RESULTS 64/234 (27%) patients belonged to Lip- group and 170/234 (73%) patients were allocated to Lip+ group. Significantly more male patients (78% in Lip- vs. 63% in Lip+, p<0.05) with RAP (63% in Lip- vs. 21% in Lip+, p<0.001) were observed in the Lip- group. EPIC was significantly lower in Lip- group compared to Lip+ group (3(IQR 2-5) vs. 2(IQR 1-3), p<0.001). Mortality from pancreatic and non-pancreatic causes was comparable in Lip- and Lip+ group (pancreatic causes: 9% vs. 6%, p=0.60; nonpancreatic causes: 8% vs. 5%, p=0.58). CONCLUSIONS 27% of all patients with AP presented without threefold increase of lipase levels. Thus, they would be underdiagnosed without confirming CECT, which revealed significantly lower counts of pleural effusions and ascites. Male patients with RAP were found significantly more often among the Lip- group. Hence, they would benefit the most from CECT for diagnosing AP.

Lateralized Odontoid in Plain Film Radiography: Sign of Fractures? – A Comparison Study with MDCT

PURPOSE To evaluate X-ray standards for the detection of odontoid fractures. SUMMARY OF BACKGROUND DATA Cervical spine fractures are a common finding in emergency medicine, accounting for 1-3% of injuries. Involvement of the C1/C2 complex is found in 25% of cases, affecting the odontoid peg in 55-80%. Regarding the consequences of missed fractures, radiographic techniques built the groundwork for further treatment procedures. As standardized X-ray measurements have not been established, the incidence of unrecognized cervical spine fracture is expected to be up to 20%. The establishment of X-ray-based guidelines is also limited by the presumed low specificity and sensitivity of distance measurements caused by rotational distortion which leads to a rising popularity of CT. MATERIALS AND METHODS 79 (age 60 ± 26 yrs) patients with lateralization of the odontoid process on conventional plain film radiography (anteroposterior, lateral, and open mouth odontoid process view projection) were examined. The distance between the odontoid process and lateral mass of C1, angles of vertical odontoid line and basis of C2 were measured in the ap view. In the lateral view, dorsal alignment and atlantodental distance were assessed. MDCT examinations were used as a reference. Discriminatory power test was applied to assess significance. RESULTS 8/79 (10.1%) odontoid process fractures were found. Diagnosis was achieved on conventional radiographs in 6 patients. Neither distance and angle measurements between odontoid and C1 nor the dorsal alignment of the vertebral bodies differed significantly between healthy and affected patients. CONCLUSION Decentralization of the odontoid process is not necessarily an indirect sign for its fracture. In patients with suspected injury of the odontoid process, an MDCT scan might be the method of choice to rule out a fracture. KEY POINTS Due to the wide physiological variety of odontoid process position, even a detailed metric analysis of cervical alignment and odontoid process angulation in X-ray scans is not able to facilitate the diagnosis of odontoid process fractures. In the case of cervical spine trauma, which necessitate medical imaging, a primary MDCT scan should be the method of choice.

Clinico-radiological comparison and short-term prognosis of single acute pancreatitis and recurrent acute pancreatitis including pancreatic volumetry

Purpose The necrosis-fibrosis hypothesis describes a continuum between single attacks of acute pancreatitis (SAP), recurrent acute pancreatitis (RAP) and chronic pancreatitis (CP) with endocrine and exocrine pancreatic insufficiency. For prevention purposes we evaluated clinico-radiological parameters and pancreatic volumetry to compare SAP and RAP and provide prognostic relevance on short-term mortality, need for intervention and the hospitalization duration. Materials and methods We retrospectively investigated 225 consecutive patients (150 males, range 19-97years) with acute pancreatitis (74%SAP, 26%RAP) according to the revised Atlanta classification. All patients received an intravenous contrast-enhanced CT after a median time of 5 (IQR 5–7) days after onset of symptoms. Two experienced observers rated the severity of AP by 3 CT scores (CTSI, mCTSI, EPIC). Moreover, total pancreatic volumes and additional parenchymal necrosis volumes were assessed, when appropriate. Clinical parameters were etiology of AP, lipase on admission, CRP 48 hours after admission (CRP48), and the presence of organ dysfunction, assessed by the modified Marshall score. The modified Marshall score included systolic blood pressure, serum creatinine, and the ratio of arterial oxygen partial pressure to fractional inspired oxygen (PaO2/FiO2 ratio) and was assessed on admission and 48 hours after admission to find patients with persistent organ failure. Outcome parameters were total hospitalization duration, short-term mortality and need for intervention. Results Lipase, CRP48, etiology of AP, EPIC, PaO2/FiO2 ratio, and the presence of a pleural effusion differed significantly in both groups (p<0.05). In 109 patients with interstitial edematous AP, the total pancreatic volume was significantly smaller in patients with RAP compared to those with SAP (69±35cm3; (RAP) vs 106±45cm3; (SAP), p<0.001). All outcome parameters including the mortality rates (SAP vs. RAP: 15% vs. 7%) were comparable in both groups (p>0.05). In the necrotizing RAP group, only the necrotic volume correlated significantly with total hospitalization time (r = 0.72, p<0.001), whereas the systolic blood pressure was the only, but weak predictor for short-term mortality (β-coefficient: -0.05, p = 0.03) and the need for intervention (β-coefficient: -0.02, p = 0.048) in the total RAP group. In patients with SAP, the modified Marshall score was the strongest predictor of short-term mortality, followed by the mCTSI on multivariate logistic regression (Marshall score: β-coefficient: 1.79, p<0.001; mCTSI: β-coefficient: 0.40, p<0.001). CTSI was the best predictor for required intervention in necrotizing SAP (β-coefficient: 0.46, p<0.001), followed by the volume of intrapancreatic necrosis (β-coefficient: 0.17, p = 0.03). Conclusion Total pancreatic volume differed significantly between interstitial RAP and SAP and intrapancreatic necrosis volume revealed prognostic value for the total hospitalization duration in necrotizing RAP. Although all outcome parameters were comparable between SAP and RAP, only systolic blood pressure and pancreatic volumetry were prognostic in RAP. In SAP, only the modified Marshall score and mCTSI revealed prognostic value for short-term mortality, whereas CTSI was predictive for the need for intervention.

Prospective comparison of diffusion-weighted MRI and dynamic Gd-EOB-DTPA-enhanced MRI for detection and staging of hepatic fibrosis in primary sclerosing cholangitis

PurposeTo assess the diagnostic value of multiparametric magnetic resonance imaging (MRI) including dynamic Gd-EOB-DTPA-enhanced (DCE) and diffusion-weighted (DW) imaging for diagnosis and staging of hepatic fibrosis in primary sclerosing cholangitis (PSC) using transient elastography as a standard reference.Material and methodsMultiparametric MRI was prospectively performed on a 3.0-Tesla scanner in 47 patients (age 43.9±14.3 years). Transient elastography derived liver stiffness measurements (LSM), DCE-MRI derived parameters (hepatocellular uptake rate (Ki), arterial (Fa), portal venous (Fv) and total (Ft) blood flow, mean transit time (MTT), and extracellular volume (Ve)) and the apparent diffusion coefficient (ADC) were calculated. Correlation and univariate analysis of variance with post hoc pairwise comparison were applied to test for differences between LSM derived fibrosis stages (F0/F1, F2/3, F4). ROC curve analysis was used as a performance measure.ResultsBoth ADC and Ki correlated significantly with LSM (r= -0.614; p<0.001 and r= -0.368; p=0.01). The ADC significantly discriminated fibrosis stages F0/1 from F2/3 and F4 (p<0.001). Discrimination of F0/1 from F2/3 and F4 reached a sensitivity/specificity of 0.917/0.821 and 0.8/0.929, respectively. Despite significant inter-subject effect for classification of fibrosis stages, post hoc pairwise comparison was not significant for Ki (p>0.096 for F0/1 from F2/3 and F4). LSM, ADC and Ki were significantly associated with serum-based liver functional tests, disease duration and spleen volume.ConclusionDW-MRI provides a higher diagnostic performance for detection of hepatic fibrosis and cirrhosis in PSC patients in comparison to Gd-EOB-DTPA-enhanced DCE-MRI.Key Points• Both ADC and hepatocellular uptake rate (Ki) correlate significantly with liver stiffness (r= -0.614; p<0.001 and r= -0.368; p=0.01).• The DCE-imaging derived quantitative parameter hepatocellular uptake rate (Ki) fails to discriminate pairwise intergroup differences of hepatic fibrosis (p>0.09).• DWI is preferable to DCE-imaging for discrimination of fibrosis stages F0/1 to F2/3 (p<0.001) and F4 (p<0.001).

Diagnostic prediction of complicated appendicitis by combined clinical and radiological appendicitis severity index (APSI)

ObjectivesTo develop a routinely applicable severity index for the management of acute appendicitis in adults using combined clinical and radiological parameters and retroperitoneal space planes (RSP).MethodsTwo hundred consecutive patients with histologically proven acute appendicitis and available presurgical CT scans were analysed retrospectively. Two radiologists assessed all CT scans for morphologic sings of appendicitis and six RSP. Clinical parameters were age, body temperature, C-reactive protein (CRP), white blood cell count, and duration of symptoms. Radiological parameters were appendix diameter and wall thickness, periappendiceal fat stranding and fluid, intraluminal and extraluminal air, thinning of appendiceal wall, caecal wall thickening, appendicolith and abscess formation.ResultsOne hundred and three patients (51%) had histologically proven complicated appendicitis. Based on three clinical (age ≥52 years, body temperature ≥37.5°C, duration of symptoms ≥48 h) and four computed tomography (CT) findings (appendix diameter ≥14 mm, presence of periappendiceal fluid, extraluminal air, perityphlitic abscess), the APSI was developed using regression coefficients of multivariate logistic regression analyses with a maximum of 10 points. A score of ≥4 points predicted complicated appendicitis with a positive predictive value of 92% and a negative predictive value of 83%. Substantial to excellent interobserver agreement was found for the four radiological parameters of the APSI [intraclass correlation coefficient (ICC), 0.78-0.83]. The RSP evaluation presented no added value for the diagnosis of complicated appendicitis.ConclusionsUsing APSI, an accurate and simple prediction of complicated appendicitis in adults was possible. The RSP count was not useful for the diagnosis of complicated appendicitis.Key points• Appendicitis severity score provides an accurate and simple prediction of complicated appendicitis• Appendicitis severity score ≥4 accurately predicted complicated appendicitis (PPV 92%;NPV 83%)• Evaluation of retroperitoneal space planes was not useful in diagnosing complicated appendicitis

Gadolinium-based relative contrast enhancement in primary sclerosing cholangitis: additional benefit for clinicians?

AIM To evaluate the benefit of extracellular gadolinium-based contrast agent (GBCA) enhanced magnetic resonance imaging (MRI) in addition to conventional non-enhanced T2-weighted imaging (WI) for quantification of inflammatory or fibrotic alterations in the liver parenchyma of patients with primary sclerosing cholangitis (PSC). MATERIAL AND METHODS MRI (3 T) examinations were reviewed retrospectively by two radiologists in 27 PSC patients (age 42.9±15.6 years), and 19 controls. Regions of interest (ROIs) were drawn onto T2 hyperintense and T2 isointense areas and copied to section position matched non-enhanced and delayed-phase contrast-enhanced T1WI. Signal intensities (SI) obtained from ROIs of the multiphase T1WI were used to calculate relative liver enhancement (RLE). The interobserver agreement of RLE and quantified T2 signal was calculated using Bland-Altman analysis. RLE assessed for both T2 hyperintense (RLEhyper) and T2 isointense (RLEiso) areas were compared in patients and controls (RLEhealthy). RESULTS The interobserver agreement of RLE in affected hyperintense areas (bias -0.77, limits of agreement -51.7 to 50.1) was superior to the quantification of T2 signal only in these areas (bias -3.35, limits of agreement -162.4 to 155.7). The RLEhyper (86.2±9.7%) was higher than the RLEiso (59.8±6.2%, p=0.03) and the RLEhealthy (53.2±2.7%, p=0.002). The mean RLEiso was not significantly different from the RLEhealthy (p=0.3). CONCLUSION The extracellular gadolinium-based RLE of T2 hyperintense areas could be a useful add-on for routine follow up MRI in the detection of early inflammatory changes, possibly preceding formation of fibrotic scarring in PSC patients, if validated in larger cohorts.