Safe and Informed Use of Gadolinium-Based Contrast Agent in Body Magnetic Resonance Imaging: Where We Were and Where We Are.

Gadolinium-based contrast agents (GBCAs) have helped to improve the role of magnetic resonance imaging (MRI) for the diagnosis and treatment of diseases. There are currently nine different commercially available gadolinium-based contrast agents (GBCAs) that can be used for body MRI cases, and which are classifiable according to their structures (cyclic or linear) or biodistribution (extracellular-space agents, target/specific-agents, and blood-pool agents). The aim of this review is to illustrate the commercially available MRI contrast agents, their effect on imaging, and adverse reaction on the body, with the goal to lead to their proper selection in different clinical contexts. When we have to choose between the different GBCAs, we have to consider several factors: (1) safety and clinical impact; (2) biodistribution and diagnostic application; (3) higher relaxivity and better lesion detection; (4) higher stability and lower tissue deposit; (5) gadolinium dose/concentration and lower volume injection; (6) pulse sequences and protocol optimization; (7) higher contrast-to-noise ratio at 3.0 T than at 1.5 T. Knowing the patient's clinical information, the relevant GBCAs properties and their effect on body MRI sequences are the key features to perform efficient and high-quality MRI examination.

Assessing the necessity of intravenous contrast for computed tomography in the acute undifferentiated abdomen.

INTRODUCTION: Undifferentiated abdominal pain in the emergency setting is frequently investigated with an intravenous contrast enhanced CT as a first line diagnostic test. However, global contrast shortages restricted the use of contrast for a period in 2022, altering standard practice with many scans performed without intravenous contrast. Whilst IV contrast can be useful to assist with interpretation, its necessity in the setting of acute undifferentiated abdominal pain is not well described, and its use comes with its own risks. This study aimed to assess the shortcomings of omitting IV contrast in an emergency setting, by comparing the rate of CT scans with "indeterminate" findings with and without the use of IV contrast. METHODS: Data from presentations to a single centre emergency department for undifferentiated abdominal pain prior to and during contrast shortages in June 2022 were retrospectively compared. The primary outcome was the rate of diagnostic uncertainty, where the presence or absence of intra-abdominal pathology could not be ascertained. RESULTS: 12/85 (14.1%) of the unenhanced abdominal CT scans provided an uncertain result, compared with 14/101 (13.9%) of control cases performed with intravenous contrast (P = 0.96). There were also similar rates of positive and negative findings between the groups. CONCLUSION: Omitting intravenous contrast for abdominal CT in the setting of undifferentiated abdominal pain demonstrated no significant difference in the rate of diagnostic uncertainty. There are significant potential patient, fiscal and societal benefits as well as potential improvements to emergency department efficiency with the reduction of unnecessary intravenous contrast administration.

Imaging Evaluation of the Living Liver Donor: A Systems-Based Approach.

Liver transplant is the definitive treatment of end-stage liver disease and early hepatocellular carcinoma. The number of liver transplant surgeries done is highly affected by the number and availability of deceased donor organs. Living donor liver transplantation has emerged as an alternative source of donors, increasing the availability of organs for transplant. Many factors must be considered when choosing living donor candidates to maintain a high level of donor safety and organ survival. To that end, potential donors undergo a rigorous pre-donation workup.

Application of Pharmacokinetic Modeling to Characterize Hepatobiliary Disposition of Imaging Agents and Alterations due to Liver Injury in Isolated Perfused Rat Livers.

BACKGROUND: Understanding the impact of altered hepatic uptake and/or efflux on the hepatobiliary disposition of the imaging agents [99mTc]Mebrofenin (MEB) and [153Gd]Gadobenate dimeglumine (BOPTA) is important for proper estimation of liver function. METHODS: A multi-compartmental pharmacokinetic (PK) model describing MEB and BOPTA disposition in isolated perfused rat livers (IPRLs) was developed. The PK model was simultaneously fit to MEB and BOPTA concentration-time data in the extracellular space, hepatocytes, bile canaliculi, and sinusoidal efflux in livers from healthy rats, and to BOPTA concentration-time data in rats pretreated with monocrotaline (MCT). RESULTS: The model adequately described MEB and BOPTA disposition in each compartment. The hepatocyte uptake clearance was much higher for MEB (55.3 mL/min) than BOPTA (6.67 mL/min), whereas the sinusoidal efflux clearance for MEB (0.000831 mL/min) was lower than BOPTA (0.0127 mL/min). The clearance from hepatocytes to bile (CLbc) for MEB (0.658 mL/min) was similar to BOPTA (0.642 mL/min) in healthy rat livers. The BOPTA CLbc was reduced in livers from MCT-pretreated rats (0.496 mL/min), while the sinusoidal efflux clearance was increased (0.0644 mL/min). CONCLUSION: A PK model developed to characterize MEB and BOPTA disposition in IPRLs was used to quantify changes in the hepatobiliary disposition of BOPTA caused by MCT pretreatment of rats to induce liver toxicity. This PK model could be applied to simulate changes in the hepatobiliary disposition of these imaging agents in rats in response to altered hepatocyte uptake or efflux associated with disease, toxicity, or drug-drug interactions.

Extramedullary hematopoiesis (EMH) in the liver allograft presenting with a mass-like lesion.

This is a rare case of extramedullary hematopoiesis (EMH) presenting as a mass-like lesion in liver allograft. Our patient was a 57-year-old woman who had undergone liver transplantation due to hepatic epithelioid hemangioendothelioma. She presented with an ill-defined hypoechoic lesion on ultrasound which showed features of focal EMH on pathologic examinations. While transient intrahepatic hematopoiesis has been reported in liver transplant patients, focal EMH mass lesion is a rarely encountered phenomenon. Therefore, focal EMH may need to be considered as a differential diagnosis when encountering a mass in post liver transplant patients.

Liver PET Reloaded: Automated Synthesis of [68Ga]Ga-BP-IDA for Positron Imaging of the Hepatobiliary Function and First Clinical Experience.

Hepatobiliary scintigraphy is a well-established nuclear imaging method for evaluating liver function and displaying the biliary system, but the spatial and temporal resolution is limited, and, there is still no established PET equivalent. Adapted from the work of Schuhmacher et al. in 1983, the production of a 68Gallium-labeled substitute, tetrabromophthalein ([68Ga]Ga-BP-IDA), was undertaken according to current Good Manufacturing Practice (GMP) standards and proved feasible and reproducible. PET/CT with the radiotracer was performed in two complex patients with hepatocellular carcinoma in preparation for transarterial radioembolization. Due to its high spatial and temporal resolution, localization of areas with impaired liver function and visualization of the biliary system were possible. We could demonstrate that this 68Gallium-labeled, IDA-based PET tracer is feasible and could advance hepatic and biliary function PET imaging.

Rare case of intrahepatic splenosis masquerading as malignancy.

A 54-year-old man presented with abdominal pain and a history of post-traumatic splenectomy 33 years prior, imaging revealed an incidental hepatic mass.

Comparison of Clinical and Radiologic Findings Between Perforated and Non-Perforated Choledochal Cysts in Children.

OBJECTIVE: To compare the clinical and radiologic findings between perforated and non-perforated choledochal cysts in children. MATERIALS AND METHODS: Fourteen patients (mean age ± standard deviation, 1.7 ± 1.2 years) with perforated choledochal cysts (perforated group) and 204 patients (3.6 ± 3.8 years) with non-perforated choledochal cysts (non-perforated group) were included between 2000 and 2019. All patients underwent choledochal cyst excision after ultrasound, CT, or MR cholangiopancreatography. Relevant data including demographics, clinical symptoms, laboratory findings, imaging findings, and outcomes were analyzed. Statistical differences were compared using the Mann-Whitney U test and Fisher's exact test. RESULTS: Choledochal cyst perforation occurred only in children under the age of 4 years. Acute symptoms, including fever (p < 0.001), were more common in the perforated group than in the non-perforated group. High levels of white blood cells (p = 0.004), C-reactive protein (p < 0.001), and serum amylase (p = 0.002), and low levels of albumin (p < 0.001) were significantly associated with the perforated group. All 14 patients with perforated choledochal cysts had ascites, whereas only 16% (33/204) of patients in the non-perforated group had ascites (p < 0.001). In the subgroup of patients who had ascites, a large amount of ascites (p = 0.001), increase in the amount of ascites in a short time (p < 0.001), complex ascites (p < 0.001), and perihepatic pseudocysts (p < 0.001) were more common in the perforated group than in the non-perforated group. CONCLUSION: Children with perforated choledochal cysts have characteristic clinical and radiologic findings compared to those with non-perforated choledochal cysts. In young children with choledochal cysts, perforation should be differentiated in cases with acute symptoms, laboratory abnormalities, and characteristic ascites findings.

Haemobilia secondary to an arterio-biliary fistula: A rare complication of intra-operative microwave ablation of hepatocellular carcinoma.

A rare case of arterio-biliary fistula and haemobilia complicating intra-operative microwave ablation of hepatocellular carcinoma in a 58-year-old woman with cirrhosis.

Abdominal Organ Enhancement in Dynamic MRI using 1 M Gadobutrol vs 0.5 M Meglumine Gadoterate in Liver of Hemangioma Patients.

BACKGROUND: The utility of gadobutrol (GAD) which is higher r1 value contrast media for evaluating abdominal solid organ have not been fully evaluated. OBJECTIVE: To compare the contrast enhancement of abdominal organs on dynamic MRI using 0.1 mmol/kg 1.0 M GAD or 0.5 M meglumine gadoterate (MG) in patients with a liver hemangioma. METHODS: A phantom study was performed at different concentrations (0.05, 0.1, 0.3, 0.5, 0.7, 0.9, 1.0, 5.0 and 10 mmol/L) of GAD and MG. Sixty-two patients with a liver hemangioma were enrolled. Contrast media was injected at a rate of 2 mL/s followed by 40 mL of saline. Two arterial phases, a portal phase and an equilibrium phase were obtained. One certified radiologist set regions of interest on the abdominal aorta, liver, pancreas, spleen and the liver hemangioma. The relative enhancement ratio (RER) was calculated. RESULTS: In the phantom study the signal intensity of both contrast media was similar at lower concentrations. However, the signal intensity of MG was higher at concentrations of more than 5.0 mmol/L. In the clinical study the RER of the abdominal viscera during the portal and equilibrium phases was higher with GAD. The hemangioma had a higher equilibrium phase enhancement with GAD. The aortic RER was equivalent during all phases and the liver RER during the 2nd arterial phase was higher with GAD. The arterial phase during GAD imaging might have been measured later than was optimal. CONCLUSION: When the same injection protocol was used for an abdominal dynamic MRI, arterial phase imaging was late when GAD was used. The higher T1 relaxation value was significantly higher in the abdominal viscera during the portal and equilibrium phases, while the liver hemangioma also had significantly higher contrast enhancement during the equilibrium phase. CLINICAL TRIAL REGISTRATION NUMBER: 3186.

Advanced hepatic vasculobiliary imaging segmentation and 3D reconstruction as an aid in the surgical management of high biliary stenosis.

BACKGROUND: Three-dimensional (3D) models are increasingly used to help surgeons, guiding them through the complex hepatic vasculobiliary anatomy. The biliary tract is a relatively untapped territory with only a few case reports described in medical literature. Our aim is to present an innovative 3D reconstruction methodology for biliary imaging and surgical planning, applied to a case of iatrogenic biliary stricture, with fusion of segmented CT and MRI images. CASE PRESENTATION: A selected case of Bismuth type III iatrogenic biliary stenosis for 3D planning. CT and MR studies were acquired with dedicated protocols for segmentation. Two radiologists performed segmentation and 3D model post-processing, fusing both imaging techniques to faithfully render the anatomical structures. Measurements of anatomical landmarks were taken in both the CT/MRI and the 3D model to assure its accuracy and differences in measurement were calculated. The 3D model replicates anatomical structures and pathology with high accuracy, with only 2.2% variation between STL, CT and MRI measurements. The model was discussed with the surgical team and used in the surgical planning, improving confidence in this delicate procedure, due to the detailed prior knowledge of the patient's anatomy. CONCLUSION: Three-dimensional reconstructions are a rapidly growing area of research with a significant impact in the personalized and precision medicine. The construction of 3D models that combine vascular and biliary anatomy, using different imaging techniques, respectively CT and MRI, will predictably contribute to a more rigorous planning of complex liver surgeries.

Primary hepatic neuroendocrine tumor: A rare entity.

Liver is the most common site for neuroendocrine metastasis. However, primary neuroendocrine tumor is a rare focal hepatic lesion with a better prognosis than hepatocellular carcinoma and other malignant hepatic lesions. We present a case of primary hepatic neuroendocrine tumor in a 38-year-old female patient with a radiological diagnosis of atypical focal hepatic lesion, and a confirmed diagnosis on histopathology. Few radiology features like predominant cystic component with absence of focal lesion at any other site, aids the imaging diagnosis of primary hepatic neuroendocrine tumor.

Improving Hepatobiliary Imaging as a Physiologic Test with Superior Clinical Outcomes.

This study aims at prospectively evaluating the difference in the effect of cholecystokinin (CCK) and half-and-half milk (HHM) administered in the same patient on gallbladder contractility and correlation with clinical outcomes. Upon gallbladder visualization during standard hepatobiliary imaging, 0.02 µg/kg of CCK was injected over 3 min, and additional 30 min of dynamic imaging was obtained. Patients with gallbladder ejection fraction (GBEF) <35% after CCK were administered 8 oz of HHM followed by 30 min of imaging. The GBEF was recalculated. The number of patients whom GBEF changed from below 35% (abnormal) after CCK to above 35% (normal) after HHM was recorded. Follow-up of the clinical outcome at 6 months was performed. Fifty patients with abnormal GBEF were prospectively included. The average GBEF after CCK was 14.7% ± 8.5% and after HHM was 30.7% ± 20.8%. The average increase in GBEF with HHM was 16.0% ± 22.2%. The GBEF changed from abnormal to normal in 17 patients (34%). The remaining 33 patients remained abnormal. Clinical outcomes at 6 months were available in 47 patients. Cholecystectomy was performed in 60% of patients with abnormal GBEF with CCK and HHM with resolution or improvement of pain. Two of 16 patients (12%) with abnormal GBEF after CCK but normal after HHM had cholecystectomies with pain improvement, while 8 out of these patients (50%) were diagnosed and treated with other disorders and improved. Hepatobiliary imaging with HHM stimulation is a superior physiologic test which can lower the number of unnecessary cholecystectomies and misdiagnoses as functional cholecystitis.

Budd-Chiari Syndrome and hepatic regenerative nodules: Magnetic resonance findings with emphasis of hepatobiliary phase.

Budd-Chiari syndrome (BCS) is a disorder with numerous causes that is a result of hepatic outflow obstruction, in the absence of right heart failure or constrictive pericarditis. Acute Budd-Chiari syndrome is uncommon and clinically characterized by ascites, hepatomegaly, and hepatic insufficiency. In the majority of cases, patients present with chronic BCS, showing a dysmorphic liver disease with variable fibrosis deposition. In chronic Budd-Chiari syndrome, hepatocellular carcinoma (HCC) and benign regenerative nodules (called large regenerative nodules or FNH-like lesions) have been described in the literature. Very few studies have reported magnetic resonance imaging (MRI) findings about these nodules, using hepatobiliary contrast medium. The aim of our review is to describe the magnetic resonance imaging findings of hepatic regenerative nodules in BCS, with emphasis on the hepatobiliary phase, and to compare the imaging features of benign nodules with those of HCC.

Early US findings of biliary atresia in infants younger than 30 days.

PURPOSE: To investigate and compare ultrasound (US) findings for the diagnosis of biliary atresia (BA) in infants younger than 30 days with those of infants older than 30 days. MATERIALS AND METHODS: From 2000 to 2015, we reviewed hepatobiliary US images in 12 BA infants younger than 30 days (younger BA group) and 62 BA infants older than 30 days (older BA group) before Kasai procedure. Eight (67%) of younger BA group underwent follow-up US examinations before Kasai procedure. Our review of the images focused on triangular cord sign, gallbladder (GB) abnormalities, vascular changes, and signs of portal hypertension. RESULTS: The triangular cord sign was present in 17% of younger BA group and in 56% of older BA group (P=.024). GB abnormalities were commonly identified in both groups. The hepatic artery diameter was significantly smaller in younger BA group than in older BA group (P<.001). Signs of portal hypertension were less common in younger BA group (17%) than in older BA group (84%) (P<.001). Follow-up US of two infants in younger BA group showed a new appearance of the triangular cord sign. CONCLUSION: BA infants younger than 30 days showed atypical US findings compared with those older than 30 days. KEY POINTS: • BA infants younger than 30 days show atypical US findings. • GB abnormalities were common in both younger and older BA group. • Subsequent US examination may be helpful to diagnose BA in young infants.

Dumbbell Gallbladder Cholecystitis on Tc-99m Diisopropyliminodiacetic acid Hepatobiliary Imaging.

We present a case of a 79-year-old immunocompromised female admitted for abdominal pain and sepsis, who had an abdominal computed tomography (CT) showing distal gallbladder fundus wall thickening, pericholecystic edema, and a right posteroinferior hepatic abscess. Subsequent hepatobiliary scintigraphy with Tc-99m diisopropyliminodiacetic acid showed gallbladder filling of the proximal gallbladder fundus, yet no radiotracer filling of the distal gallbladder fundus. Further correlation with the initial CT showed a partial gallbladder stricture and a resultant altered morphology resembling a dumbbell-shaped gallbladder. Percutaneous cholangiogram also confirmed this dumbbell morphology. Nonfilling of radiotracer into the distal end of the dumbbell gallbladder correlating with CT findings of focal gallbladder inflammation indicated that there was a focal inflammation suggesting a distal dumbbell gallbladder cholecystitis. This case demonstrates a unique finding of focal inflammatory pathology involving an anatomic variant - the dumbbell-shaped gallbladder, and the challenges this anatomic variant presents in hepatobiliary scintigraphy image interpretation.

Duodenal Obstruction on 99mTc-DISIDA Cholescintigraphy: A Noninvasive Approach to Bowel Obstruction Diagnosis.

We present a case study of a 56-y-old man who was admitted with acute abdominal pain and was found to have retroperitoneal hematoma from a ruptured duodenal aneurysm. 99mTc-diisopropyliminodiacetic acid cholescintigraphy showed incidental absent transit of radiotracer into the distal duodenum and severe enterogastric reflux, thought to be secondary to duodenal obstruction from the hematoma. Findings were confirmed on esophagogastroduodenoscopy, and the patient improved after subsequent gastrojejunostomy.

Morphine-Modified Hepatobiliary Scanning Protocol for the Diagnosis of Acute Cholecystitis.

OBJECTIVE: We report a morphine-modified hepatoiminodiacetic acid (HIDA) scanning protocol that uses 2 mg of morphine IV push at the bedside as a pretreatment. We compared this protocol with the original HIDA scanning protocol, which included delayed imaging for up to 4 hours without the use of morphine. Moreover, we contrast our results with the results of studies in the literature. MATERIALS AND METHODS: We retrospectively reviewed the charts of inpatients who underwent HIDA scanning for the diagnosis of acute cholecystitis between 2003 and 2013. The study group consisted of 374 HIDA studies of 365 patients who received 2 mg of morphine IV push at bedside and then underwent dynamic imaging for 1 hour using 222 MBq of 99mTc-mebrofenin. No delayed images were obtained. The control group consisted of 232 studies of 227 patients who underwent conventional HIDA scanning using our standard protocol with delayed imaging and without morphine. Either strict pathologic criteria or the results of a percutaneous gallbladder drainage procedure were used for the confirmation of acute cholecystitis. RESULTS: The true-negative rate in the study group was 77% and in the control group, 72%. The positive predictive value in the study group was 81% and in the control group, 45%. The negative predictive value in the study group was 98% and in the control group, 99%. The accuracy in the study group was 95% and in the control group, 84%. The sensitivity in the study group was 93% and in the control group, 93%. The specificity in the study group was 95% and in the control group, 83%. The differences in the true-negative rate, accuracy, specificity, and positive predictive value of the morphine-modified protocol used for the study group and the original protocol used for the control group were statistically significant (p < 0.0005). CONCLUSION: Pretreatment using 2 mg of IV morphine at bedside before radionuclide imaging is superior to routine HIDA scanning with only delayed images for the diagnosis of acute cholecystitis. The results of our pretreatment morphine-modified protocol are comparable to those reported in the literature for posttreatment morphine-augmented protocols.

Synthesis, in vitro and in vivo small-animal SPECT evaluation of novel technetium labeled bile acid analogues to study (altered) hepatic transporter function.

INTRODUCTION: Hepatobiliary transport mechanisms are crucial for the excretion of substrate toxic compounds. Drugs can inhibit these transporters, which can lead to drug-drug interactions causing toxicity. Therefore, it is important to assess this early during the development of new drug candidates. The aim of the current study is the (radio)synthesis, in vitro and in vivo evaluation of a technetium labeled chenodeoxycholic and cholic acid analogue: [(99m)Tc]-DTPA-CDCA and [(99m)]Tc-DTPA-CA, respectively, as biomarker for disturbed transporter functionality. METHODS: [99mTc]-DTPA-CDCA([(99m)Tc]-3a) and [99mTc]-DTPA-CA ([(99m)Tc]-3b) were synthesized and evaluated in vitro and in vivo. Uptake of both tracers was investigated in NTCP, OCT1, OATP1B1, OATP1B3 transfected cell lines. Km and Vmax values were determined and compared to [(99m)Tc]-mebrofenin ([(99m)Tc]-MEB). Efflux was investigated by means of CTRL, MRP2 and BSEP transfected inside-out vesicles. Metabolite analysis was performed using pooled human liver S9. Wild type (n=3) and rifampicin treated (n=3) mice were intravenously injected with 37MBq of tracer. After dynamic small-animal SPECT and short CT acquisitions, time-activity curves of heart, liver, gallbladder and intestines were obtained. RESULTS: We demonstrated that OATP1B1 and OATP1B3 are the involved uptake transporters of both compounds. Both tracers show a higher affinity compared to [(99m)Tc]-MEB, but are in a similar range as endogenous bile acids for OATP1B1 and OATP1B3. [(99m)Tc]-3a shows higher affinities compared to [(99m)Tc]-3b. Vmax values were lower compared to [(99m)Tc]-MEB, but in the same range as endogenous bile acids. MRP2 was identified as efflux transporter. Less than 7% of both radiotracers was metabolized in the liver. In vitro results were confirmed by in vivo results. Uptake in the liver and efflux to gallbladder + intestines and urinary bladder of both tracers was observed. Transport was inhibited by rifampicin. CONCLUSION: The involved transporters were identified; both tracers are taken up in the hepatocytes by OATP1B1 andOATP1B3 with Km and Vmax values in the same range as endogenous bile acids and are secreted into bile canaliculi via MRP2. Dynamic small-animal SPECT imaging can be a useful noninvasive method of visualizing and quantifying hepatobiliary transporter functionality and disturbances thereof in vivo, which could predict drug pharmacokinetics.

Combined gadoxetic acid and gadofosveset enhanced liver MRI: A feasibility and parameter optimization study.

PURPOSE: Demonstration of feasibility and protocol optimization for the combined use of gadofosveset trisodium with gadoxetic acid for delayed T1-weighted liver MRI. METHODS: Eleven healthy volunteers underwent hepatobiliary phase imaging at 3 Tesla (T) using gadoxetic acid. Multiple breathheld T1-weighted three-dimensional spoiled gradient echo sequences were performed at varying flip angles before and after injection of gadofosveset. Signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) were measured to determine optimal T1-weighting. Examples of three patients with focal liver lesions were acquired. RESULTS: The addition of gadofosveset to the hepatobiliary phase of gadoxetic acid renders vessels isointense to liver tissue at low flip angles due to increased vessel SNR (P < 0.001). The lowest CNR of liver relative to portal vein (CNR = 15; 95% confidence interval [CI]: -14-44) was observed at a 10º flip angle. The highest CNR of liver relative to muscle (CNR = 214; 95% CI: 191-237) was observed at a 20º flip angle. The combined enhancement leads to homogenously enhanced liver tissue and liver vasculature. Cysts were detected in three volunteers and metastases were detected in two patients. In these anecdotal cases the cysts and metastases stood out as conspicuous focal hypointensities on combined gadoxetic acid and gadofosveset enhanced images. CONCLUSION: Combined gadoxetic acid and gadofosveset enhanced liver MRI is feasible, with low flip angles minimizing contrast between vessels and liver. Further clinical studies are needed to confirm that low flip angles provide an optimal combination of sensitivity and specificity for lesion detection in patients.