Contrast Media in Pregnant and Lactating Patients, From the AJR Special Series on Contrast Media.

IV contrast media improve the diagnostic power of radiology examinations. These media include gadolinium-based contrast media and iron-oxide nanoparticles for MRI, iodinated contrast material for CT, microbubbles for ultrasound, and radiopharmaceuticals for nuclear medicine. As for all medications, contrast media carry risks, which may be heightened in the conditions of pregnancy and lactation. Radiologists must understand the potential risks from contrast media exposure to the pregnant patient, fetus, and nursing infant, as well as understand these administrations' impact on examinations' clinical utility. This article reviews the available literature on these media, along with key regulatory bodies' and professional societies' current recommendations for their use, in the settings of pregnancy and lactation. This knowledge should help radiologists make well-reasoned risk-benefit analyses regarding contrast media administration and provide informed consent discussions with pregnant and nursing patients in whom contrast media administration is being considered. This information and analysis can also assist facilities in designing policies and standard operating procedures of possible clinical benefit to the pregnant patient, fetus, or nursing infant, balancing contrast media exposure considerations versus augmented diagnostic capabilities.

Risk of Acute Kidney Injury Following IV Iodinated Contrast Media Exposure: 2023 Update, From the AJR Special Series on Contrast Media.

Iodinated contrast material (ICM) has revolutionized the field of diagnostic radiology through improvements in diagnostic performance and expansion in clinical indications for radiographic and CT examinations. Historically, nephrotoxicity was a feared complication of ICM use, thought to be associated with a significant risk of morbidity and mortality. Such fears often precluded use of ICM in imaging evaluations, commonly at the expense of diagnostic performance and timely diagnosis. Over the past 20 years, the nephrotoxic risk of ICM has become a topic of debate, as more recent evidence from higher-quality studies now suggest that many cases of what was considered contrast-induced acute kidney injury (CI-AKI) were likely cases of mistaken causal attribution; most of these cases represented either acute kidney injury (AKI) caused by any of myriad other known factors that can adversely affect renal function and were coincidentally present at the time of contrast media exposure (contrast-associated AKI (CA-AKI)) or a manifestation of the normal variation in renal function that increases with worsening renal function. This review discusses the current state of knowledge on CI-AKI and CA-AKI including the incidence, risk factors, outcomes, and prophylactic strategies in the identification and management of these clinical conditions.

Intact Behavioral Expression of Contextual Fear, Context Discrimination, and Object Discrimination Memories Acquired in the Absence of the Hippocampus.

We test the hypothesis that the stability and precision of context and visual discrimination memories depend on interactions between the hippocampus (HPC) and other memory storage networks. In four experiments we tested the properties of memories acquired in the absence of the HPC. Long-Evans male rats were exclusively used in all experiments. Experiment 1 evaluated acquisition and retention of context fear memories in rats with prior partial or complete HPC damage. Confirming an earlier report (Zelikowsky et al., 2012) a very small but statistically reliable slowing in a single session of context fear conditioning was found after HPC damage. In contrast, retention of context fear memory was normal after HPC damage up to 30 d after learning. In experiment 2, we found that discrimination between a context paired with foot shocks and a different context never paired with foot shock was retained normally for 15 d. In experiment 3, we replicated the finding of intact context discrimination for at least 15 d in rats who display a significant impairment in acquisition of place learning in the Morris water task (MWT). In final experiment using an appetitive object discrimination task, we showed normal retention of the discrimination for at least 30 d after training in rats with complete HPC damage. These finding score against the idea that non HPC memory storage requires a period of interaction with HPC to establish a stable, precise memory.SIGNIFICANCE STATEMENT Contrary to expectations from systems memory consolidation, we find that in the absence of a functional hippocampus (HPC) context and visual memories are formed rapidly and exhibit normal persistence and precision. The findings suggest that the HPC is not obligatory for these features of long-term memories.

Symptoms Associated with Gadolinium Exposure (SAGE): A Suggested Term.

In this article, members of the American College of Radiology Committee on Drugs and Contrast Media propose a new term for symptoms reported after intravascular exposure to gadolinium-based contrast agents-Symptoms Associated with Gadolinium Exposure, or SAGE. This term is advocated in lieu of other proposed nomenclature that presumes a causal relationship that has not yet been scientifically verified. The purpose of this new term, SAGE, is to assist researchers and clinical providers in describing such symptoms without prematurely causally attributing them to a disease and to standardize reporting of these symptoms to allow for coherent interpretation of related studies.

Neurologic Effects of Gadolinium Retention in the Brain after Gadolinium-based Contrast Agent Administration.

Background Concerns over the neurotoxic potential of retained gadolinium in brain tissues after intravenous gadolinium-based contrast agent (GBCA) administration have led to pronounced worldwide use changes, yet the clinical sequelae of gadolinium retention remain undefined. Purpose To assess clinical and neurologic effects and potential neurotoxicity of gadolinium retention in rats after administration of various GBCAs. Materials and Methods From March 2017 through July 2018, 183 male Wistar rats received 20 intravenous injections of 2.5 mmol per kilogram of body weight (80 human equivalent doses) of various GBCAs (gadodiamide, gadobenate, gadopentetate, gadoxetate, gadobutrol, gadoterate, and gadoteridol) or saline over 4 weeks. Rats were evaluated 6 and 34 weeks after injection with five behavioral tests, and inductively coupled plasma mass spectrometry, transmission electron microscopy, and histopathology were performed on urine, serum, cerebrospinal fluid (CSF), basal ganglia, dentate nucleus, and kidney samples. Dunnett post hoc test and Wilcoxon rank sum test were used to compare differences between treatment groups. Results No evidence of differences in any behavioral test was observed between GBCA-exposed rats and control animals at either 6 or 34 weeks (P = .08 to P = .99). Gadolinium concentrations in both neuroanatomic locations were higher in linear GBCA-exposed rats than macrocyclic GBCA-exposed rats at 6 and 34 weeks (P < .001). Gadolinium clearance over time varied among GBCAs, with gadobutrol having the largest clearance (median: 62% for basal ganglia, 70% for dentate) and gadodiamide having no substantial clearance. At 34 weeks, gadolinium was largely cleared from the CSF and serum of gadodiamide-, gadobenate-, gadoterate-, and gadobutrol-exposed rats, especially for the macrocyclic agents (range: 70%-98% removal for CSF, 34%-94% removal for serum), and was nearly completely removed from urine (range: 96%-99% removal). Transmission electron microscopy was used to detect gadolinium foci in linear GBCA-exposed brain tissue, but no histopathologic differences were observed for any GBCA. Conclusion In this rat model, no clinical evidence of neurotoxicity was observed after exposure to linear and macrocyclic gadolinium-based contrast agents at supradiagnostic doses. © RSNA, 2022 Online supplemental material is available for this article.

Perforant path inputs to hippocampal subfields predict heterogeneous AMPA receptor subunit expression following rapid new spatial learning in a novel context.

The hippocampus plays a critical role in spatial learning and memory. Its contribution to support these kinds of learning and memory functions relies on synaptic plasticity and related molecular mechanisms, well documented in the long-term potentiation (LTP) literature. The present experiment measures AMPA subunit expression, in a ratio of GluA2:GluA1 as an indicator of plasticity across the hippocampus, in rats that underwent new spatial learning in either a familiar or novel context. Statistically significant effects in this plasticity indicator were observed of context condition, time after task and hippocampal subfield. Based on the strong inputs of entorhinal cortex to hippocampus, we also identified differences in GluA2:GluA1 expression trends between time points and room conditions that mirror trends in medial and lateral entorhinal cortex connectivity between new room and same room context learning, respectively. Across the transverse axis in infrapyramidal dentate gyrus, CA3 and CA1, plasticity followed entorhinal cortex projection patterns. Along the transverse axis in the suprapyramidal blade of the dentate gyrus, and along the long axis in dentate gyrus and CA3, results did not follow entorhinal cortex subregion projection patterns. These latter results may be indicative of pattern separation in the dentate gyrus and emotional triage functions of the ventral hippocampus.

Prevention of Allergic-like Reactions at Repeat CT: Steroid Pretreatment versus Contrast Material Substitution.

Background It is unclear whether steroid premedication is an effective means of preventing repeat allergic-like reactions in high-risk patients with a previous allergic-like reaction to iodinated contrast material (ICM). Purpose To compare the effectiveness of ICM substitution (ie, using iohexol in a patient with a previous iopromide reaction) with 12- and 2-hour steroid premedication for preventing repeat acute allergic-like reactions in high-risk patients. Materials and Methods This retrospective study identified all high-risk (ie, having a previous allergic-like reaction) adult and pediatric patients who underwent a contrast-enhanced CT examination at the institution from June 1, 2009, to May 9, 2017. Prophylactic treatments and repeat reactions were identified using chart review. The effectiveness of prophylactic treatments on repeat reaction rates was examined with multivariable regression models that used generalized estimating equations. Results A total of 1973 high-risk patients who underwent 4360 subsequent ICM-enhanced CT examinations were included. Of the 4360 examinations, a total of 280 allergic-like reactions occurred (6%) in 224 of the 1973 patients (11% of patients), with only 19 of 280 reactions (7%) that were more severe than the previous reaction being demonstrated. After adjustment, patients who received a different ICM with and without steroid premedication had a significantly lower rate of repeat reactions than did patients who received steroid premedication and the same ICM (same ICM and steroid premedication: 80 of 423 examinations [19%]; different ICM and no steroid premedication: 10 of 322 examinations [3%]; odds ratio [OR], 0.14 [95% CI: 0.06, 0.33]; P < .001; different ICM and steroid premedication: five of 166 patients [3%]; OR, 0.12 [95% CI: 0.04, 0.36]; P < .001). When examining the first scan only, patients who received the same ICM had a similar risk of repeat reactions regardless of whether they received steroid premedication (steroid premedication: 44 of 172 patients [26%] vs no premedication: 73 of 298 patients [25%]; OR, 1.00 [95% CI: 0.64, 1.57]; P = .99). Conclusion In this cohort, using an iodinated contrast material (ICM) substitution was more effective for preventing repeat allergic-like reactions than using steroid premedication and the same ICM that caused the previous reaction. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Davenport and Weinstein in this issue.

Use of Intravenous Gadolinium-based Contrast Media in Patients with Kidney Disease: Consensus Statements from the American College of Radiology and the National Kidney Foundation.

Inaugural consensus statements were developed and endorsed by the American College of Radiology (ACR) and the National Kidney Foundation to improve and standardize the care of patients with kidney disease who have indication(s) to receive ACR-designated group II or group III intravenous gadolinium-based contrast media (GBCM). The risk of nephrogenic systemic fibrosis (NSF) from group II GBCM in patients with advanced kidney disease is thought to be very low (zero events following 4931 administrations to patients with estimated glomerular filtration rate [eGFR] <30 mL/min per 1.73 m2; upper bounds of the 95% confidence intervals: 0.07% overall, 0.2% for stage 5D chronic kidney disease [CKD], 0.5% for stage 5 CKD and no dialysis). No unconfounded cases of NSF have been reported for the only available group III GBCM (gadoxetate disodium). Depending on the clinical indication, the potential harms of delaying or withholding group II or group III GBCM for an MRI in a patient with acute kidney injury or eGFR less than 30 mL/min per 1.73 m2 should be balanced against and may outweigh the risk of NSF. Dialysis initiation or alteration is likely unnecessary based on group II or group III GBCM administration. This article is a simultaneous joint publication in Radiology and Kidney Medicine. The articles are identical except for stylistic changes in keeping with each journal's style. Either version may be used in citing this article.

An assessment of the functional effects of amphetamine-induced dendritic changes in the nucleus accumbens, medial prefrontal cortex, and hippocampus on different types of learning and memory function.

The present experiments investigated the effects of repeated amphetamine exposure on neural networks mediating different forms of learning and memory. Different components of these networks were assessed using various functional assays. The hypothesis was that abnormal dendritic changes in nucleus accumbens, medial prefrontal cortex, and hippocampus mediated by repeated amphetamine exposure would produce impairments on forms of learning and memory dependent on neural circuits relying on these brain systems, and have little or no effect on other forms of learning not dependent on these networks. Surprisingly, the results showed that many of the dendritic changes normally found in the nucleus accumbens, prefrontal cortex, and hippocampus following repeated amphetamine exposure were reversed back to control levels following extensive multi-domain cognitive training. Learning and memory functions associated with different neural networks also appeared normal except in one case. A neural network that includes, but is not limited to, the basolateral amygdala and nucleus accumbens was dysfunctional in rats repeatedly exposed to amphetamine despite the reversal of the majority of dendritic changes in the nucleus accumbens following cognitive training. Importantly, an increase in spine density that normally occurs in these brain regions following repeated amphetamine exposure remained following extensive cognitive training, particularly in the nucleus accumbens.

Prospective multicenter assessment of patient preferences for properties of gadolinium-based contrast media and their potential socioeconomic impact in a screening breast MRI setting.

OBJECTIVE: It is unknown how patients prioritize gadolinium-based contrast media (GBCM) benefits (detection sensitivity) and risks (reactions, gadolinium retention, cost). The purpose of this study is to measure preferences for properties of GBCM in women at intermediate or high risk of breast cancer undergoing annual screening MRI. METHODS: An institutional reviewed board-approved prospective discrete choice conjoint survey was administered to patients at intermediate or high risk for breast cancer undergoing screening MRI at 4 institutions (July 2018-March 2020). Participants were given 15 tasks and asked to choose which of two hypothetical GBCM they would prefer. GBCMs varied by the following attributes: sensitivity for cancer detection (80-95%), intracranial gadolinium retention (1-100 molecules per 100 million administered), severe allergic-like reaction rate (1-19 per 100,000 administrations), mild allergic-like reaction rate (10-1000 per 100,000 administrations), out-of-pocket cost ($25-$100). Attribute levels were based on published values of existing GBCMs. Hierarchical Bayesian analysis was used to derive attribute "importance." Preference shares were determined by simulation. RESULTS: Response (87% [247/284]) and completion (96% [236/247]) rates were excellent. Sensitivity (importance = 44.3%, 95% confidence interval = 42.0-46.7%) was valued more than GBCM-related risks (mild allergic-like reaction risk (19.5%, 17.9-21.1%), severe allergic-like reaction risk (17.0%, 15.8-18.1%), intracranial gadolinium retention (11.6%, 10.5-12.7%), out-of-pocket expense (7.5%, 6.8-8.3%)). Lower income participants placed more importance on cost and less on sensitivity (p < 0.01). A simulator is provided that models GBCM preference shares by GBCM attributes and competition. CONCLUSIONS: Patients at intermediate or high risk for breast cancer undergoing MRI screening prioritize cancer detection over GBCM-related risks, and prioritize reaction risks over gadolinium retention. KEY POINTS: • Among women undergoing annual breast MRI screening, cancer detection sensitivity (attribute "importance," 44.3%) was valued more than GBCM-related risks (mild allergic reaction risk 19.5%, severe allergic reaction risk 17.0%, intracranial gadolinium retention 11.6%, out-of-pocket expense 7.5%). • Prospective four-center patient preference data have been incorporated into a GBCM choice simulator that allows users to input GBCM properties and calculate patient preference shares for competitor GBCMs. • Lower-income women placed more importance on out-of-pocket cost and less importance on cancer detection (p < 0.01) when prioritizing GBCM properties.

Acute Reactions to Gadolinium-Based Contrast Agents in a Pediatric Cohort: A Retrospective Study of 16,237 Injections.

BACKGROUND. Incidences and risk factors for acute reactions to gadolinium-based contrast agents (GBCAs) are not fully understood, particularly in pediatric patients. OBJECTIVE. The purpose of this study was to retrospectively examine allergiclike and physiologic acute reactions in pediatric patients who receive GBCAs for MRI examinations. METHODS. The study cohort consisted of all pediatric patients (age < 18 years old) who underwent an MRI examination with a GBCA at our institution from June 1, 2009, to May 9, 2017. Acute reactions were identified by medical record review and classified by severity using the American College of Radiology guidelines. Potential risk factors for reactions were examined using generalized estimating equation methods accounting for rare events. RESULTS. A total of 16,237 GBCA injections (10,141 gadodiamide injections, 4880 gadobutrol injections, and 1216 gadobenate dimeglumine injections) were administered to a study cohort of 10,190 patients (49% [7982/16,237] girls and 51% [8255/16,237] boys). Incidences of 0.10% (17/16,237) for allergiclike and 0.14% (23/16,237) for physiologic reactions were observed. No severe reactions occurred. Allergiclike reaction incidences were significantly higher with gadobenate compared with gadodiamide (0.49% vs 0.04%; p < .001) and in patients who underwent abdominal or pelvic MRI examinations (0.38%) or cardiac examinations (0.55%) compared with head examinations (0.05%; p < .001 and p = .006, respectively). Physiologic reaction incidences were significantly higher in older patients (0.25% in patients 12-17 years old vs 0.03% in patients 2 to < 12 years old; p < .001) and in patients who underwent abdominal or pelvic examinations compared with head examinations (0.38% vs 0.10%; p = .002). Of 16 MRI examinations performed in patients with a prior allergiclike reaction to GBCAs, only one resulted in a repeat reaction. CONCLUSION. In this pediatric cohort, GBCA type, patient age, and MRI type were risk factors for acute reactions. Repeat reactions were rare. CLINICAL IMPACT. Providers must weigh the risks and benefits when choosing a particular GBCA to use in their practices and must consider multiple, potentially disparate risks associated with each GBCA.

Gadolinium retention within multiple rat organs after intra-articular administration of gadolinium-based contrast agents.

OBJECTIVE: To characterize the extent of retention and biodistribution of gadolinium (Gd) following intra-articular (IA) injection of linear and macrocyclic gadolinium-based contrast agents (GBCAs) into the knee joint of a rat model. MATERIALS AND METHODS: Fifteen Wistar rats were divided into five groups and underwent fluoroscopically-guided injections of both knee joints of (1) clinical 1:200 dilution (low dose, LD) gadodiamide (linear GBCA), (2) LD gadobutrol (macrocyclic GBCA), (3) undiluted (high dose, HD) gadodiamide, (4) HD gadobutrol, and (5) saline. Gd concentrations were quantified by inductively coupled plasma mass spectrometry in (1) blood and urine samples obtained over a 72 h period and (2) knee joint tissues, brain, kidney, and bone marrow at 3 days post-injection. RESULTS: Both HD and LD gadodiamide and gadobutrol were rapidly absorbed from the joint with peak serum and urine concentration at 1 h post-injection, with relatively faster clearance of gadobutrol. All GBCA-exposed groups had detectable levels of Gd in the joint tissues, bone marrow, and/or kidneys (median tissue gadolinium range: 0.1-71 µg Gd/g tissue), with higher amounts observed with gadodiamide versus gadobutrol. Retention within brain tissues was only detected following HD gadodiamide administration but not LD gadodiamide nor HD or LD gadobutrol. CONCLUSION: There was rapid systemic absorption, redistribution, and widespread multi-organ retention of Gd following IA injection of both linear and macrocyclic GBCAs, despite substantial amounts of urinary excretion. Higher concentrations of Gd were observed with administration of gadodiamide compared to gadobutrol in most tissues and biofluids.

Has multiple trace theory been refuted?

Multiple trace theory (Nadel & Moscovitch, Current Opinion in Neurobiology, 1997, 7, 217-227) has proven to be one of the most novel and influential recent memory theories, and played an essential role in shifting perspective on systems-level memory consolidation. Here, we briefly review its impact and testable predictions and focus our discussion primarily on nonhuman animal experiments. Perhaps, the most often supported claim is that episodic memory tasks should exhibit comparable severity of retrograde amnesia (RA) for recent and remote memories after extensive damage to the hippocampus (HPC). By contrast, there appears to be little or no experimental support for other core predictions, such as temporally limited RA after extensive HPC damage in semantic memory tasks, temporally limited RA for episodic memories after partial HPC damage, or the existence of storage of multiple HPC traces with repeated reactivations. Despite these shortcomings, it continues to be a highly cited HPC memory theory.

Use of Intravenous Iodinated Contrast Media in Patients with Kidney Disease: Consensus Statements from the American College of Radiology and the National Kidney Foundation.

Intravenous iodinated contrast media are commonly used with CT to evaluate disease and to determine treatment response. The risk of acute kidney injury (AKI) developing in patients with reduced kidney function following exposure to intravenous iodinated contrast media has been overstated. This is due primarily to historic lack of control groups sufficient to separate contrast-induced AKI (CI-AKI; ie, AKI caused by contrast media administration) from contrast-associated AKI (CA-AKI; ie, AKI coincident to contrast media administration). Although the true risk of CI-AKI remains uncertain for patients with severe kidney disease, prophylaxis with intravenous normal saline is indicated for patients who have AKI or an estimated glomerular filtration rate less than 30 mL/min/1.73 m2 who are not undergoing maintenance dialysis. In individual high-risk circumstances, prophylaxis may be considered in patients with an estimated glomerular filtration rate of 30-44 mL/min/1.73 m2 at the discretion of the ordering clinician. This article is a simultaneous joint publication in Radiology and Kidney Medicine. The articles are identical except for stylistic changes in keeping with each journal's style. Either version may be used in citing this article.

Place navigation in the Morris water task results in greater nuclear Arc mRNA expression in dorsal compared to ventral CA1.

Previous work has shown that the dorsal hippocampus has greater activity than ventral regions during place navigation. Exposure to a novel context has also been found to increase hippocampal activation, possibly due to increased spatial demands. However, activation patterns in dorsal and ventral regions have not been investigated in the Morris water task (MWT), which remains the most popular assay of place memory in rodents. We measured activity in a large population of neurons across the CA1 dorsal-ventral axis by estimating nuclear Arc mRNA with stereologic systematic-random sampling procedures following changes to goal location or spatial context in the MWT in rats. Following changes to goal location or spatial context in the MWT, we did not find an effect on Arc mRNA expression in CA1. However, Arc expression was greater in the dorsal compared to the ventral aspect of CA1 during task performance. Several views might account for these observed differences in dorsal-ventral Arc mRNA expression, including task parameters or the granularity of representation that differs along the dorsal-ventral hippocampal axis. Future work should determine the effects of task differences and required memory precision in relation to dorsal-ventral hippocampal neuronal activity.

Looking beyond the standard version of the Morris water task in the assessment of mouse models of cognitive deficits.

Most studies investigating hippocampal-dependent learning and memory in mouse models of disease use the standard version of the Morris water task (MWT), in which a place is learned over several days. While useful in determining if there are learning and memory deficits, often it is not clear if memory acquisition, consolidation, or retrieval is affected. For rats, we developed a variant of the task in which we added a single-massed training session to a new location after the standard distributed version of the MWT. Using this version of the task, competition between these two spatial representations can then be assessed in a probe trial. We have found in rat models of Alzheimer's disease that this paradigm can detect subtle impairments that are often missed in the standard version of the MWT. To the best of our knowledge, MWT paradigm with a single-massed training session have never been used for mice. We sought to validate this paradigm for the use of assessing mouse models of disease. In the first two experiments, control mice did not have a preference for the new platform location, but instead with extensive training in the massed session displayed a preference for both the old and new locations. In the third experiment, a novel mouse model of Alzheimer's disease was impaired in the standard version of the MWT, but not in the massed training phase of this paradigm. Importantly, these data demonstrate that our paradigm is more informative in characterizing spatial learning and memory in mouse models of disease.

Acute Adverse Events Following Gadolinium-based Contrast Agent Administration: A Single-Center Retrospective Study of 281 945 Injections.

Background Acute allergic-like and physiologic reactions occur following administration of gadolinium-based contrast agents (GBCAs) for MRI examinations. Because these reactions are uncommon, it is challenging to compare reaction rates between GBCAs and to determine risk factors. Purpose To compare reaction rates between the four GBCAs gadodiamide, gadobutrol, gadobenate dimeglumine, and gadoterate meglumine, and to determine potential risk factors for reactions. Materials and Methods This retrospective study identified all intravenous GBCA injections for MRI examinations performed at a single institution from June 1, 2009, to May 9, 2017. Reactions were identified by reviewing records from the MRI technologist, MRI nursing staff, radiologist, emergency department, and provider. Reactions were classified as allergic-like or physiologic and as mild, moderate, or severe by using American College of Radiology criteria. GBCA reaction rates and other potential risk factors were examined by using multivariable regression models with generalized estimating equations. Results Analysis included a total of 158 100 patients (median age, 55 years [interquartile range, 40-67 years], 51% women) who received a total of 281 945 GBCA injections (140 645 gadodiamide, 94 109 gadobutrol, 39 138 gadobenate, and 8053 gadoterate). At multivariate analysis, gadobenate or gadobutrol had higher rates of allergic-like reactions compared with gadodiamide (gadobenate: odds ratio [OR], 3.9 [95% confidence interval {CI}: 3.0, 5.1]; P < .001; gadobutrol: OR, 2.3 [95% CI: 1.8, 2.9]; P < .001) or gadoterate (gadobenate: OR, 4.8 [95% CI: 1.0, 23]; P = .049; gadobutrol: OR, 2.8 [95% CI: 0.6, 14]; P = .20). Physiologic reactions were more frequently observed with gadoterate (OR, 7.7 [95% CI: 2.3, 25; P = .001), gadobenate (OR, 1.8 [95% CI: 1.3, 2.5; P < .001), and gadobutrol (OR, 1.6 [95% CI: 1.3, 2.1; P < .001) administration compared with gadodiamide. Six severe allergic-like reactions (three gadobutrol, three gadobenate) occurred requiring hospitalization. Patient age (P values .025 to < .001), sex (P < .001), location (P = .006), and MRI type (P = .003 and P = .006) were associated with acute reactions. Conclusion Gadobenate and gadobutrol are associated with higher rates of allergic-like reactions compared with gadodiamide or gadoterate, and gadoterate, gadobenate, and gadobutrol are associated with higher rates of physiologic reactions compared with gadodiamide. Patient sex, age, location, and MRI type correlate with acute reaction rates. © RSNA, 2019 Online supplemental material is available for this article.

The effects of pool shape manipulations on rat spatial memory acquired in the Morris water maze.

The Morris water maze is a popular task for examining spatial navigation and memory in rats. Historically, emphasis has been put on extramaze cues as the primary environmental feature guiding navigation and spatial memory formation. However, other features of the environment may also be involved. In this experiment, we trained rats on the spatial version of the Morris water maze over four days. A probe test was given 24 h after training, in which the shape of the pool either remained the same as during training or was changed to a different shape. Mass training of a new platform position in one training session was performed in a pool of one of these two shapes, with a second probe test being done 24 h afterward. The results showed that spatial training produces a spatial preference for the trained location in the probe test when the pool shape remains the same. However, changing the shape of the pool eliminates this preference. All groups learned the new platform position during mass training and also expressed a spatial preference for the mass-trained quadrant when tested 24 h later. The results from these experiments implicate the use of pool shape in guiding spatial navigation in the water maze and as a critical environmental feature represented in spatial memory.

Relocating cued goals induces population remapping in CA1 related to memory performance in a two-platform water task in rats.

The activity of CA1 neurons in the rodent hippocampus represents multiple aspects of learning episodes, including cue and place information. Previous reports on cue and place representation in CA1 have examined activity in single neurons and population recordings during free exploration of an environment or when actions are directed to either cue or place aspects of memory tasks. To better understand cue and place memory representation in CA1, and how these interact during goal-directed navigation, we investigated population activity in CA1 during memory encoding and retrieval in a novel water task with two visibly distinct platforms, using mRNA for immediate early genes Arc and Homer1a as markers of neural activity. After training, relocating cues to new places induces an extensive, perhaps global, remapping of the memory code that is accompanied by altered navigation and rapid learning of new cue-place information. In addition, we have found a significant relationship between the extent of reactivation and overall cue choice accuracy. These findings demonstrate an important relationship between population remapping in CA1 and memory-guided behavior.

Accumulation of Gadolinium in Human Cerebrospinal Fluid after Gadobutrol-enhanced MR Imaging: A Prospective Observational Cohort Study.

Purpose To determine whether gadolinium accumulates within cerebrospinal fluid (CSF) in patients recently exposed to the macrocyclic agent gadobutrol and identify factors that may affect this accumulation. Materials and Methods In this prospective observational cohort study, gadolinium was quantified by using inductively coupled plasma mass spectrometry of CSF samples from patients who underwent gadobutrol-enhanced magnetic resonance (MR) imaging followed by lumbar puncture within 30 days (gadobutrol group) or patients who underwent lumbar puncture without history of gadolinium-enhanced MR imaging (control group). CSF total protein level of 35 mg/dL or lower was used as a surrogate marker of an intact blood-brain barrier (BBB). Associations between gadolinium CSF concentration and patient characteristics were examined by using log (e)-linear regression models. Results A total of 82 patients (68 in gadobutrol group, 14 in control group; 42 male and 40 female patients; median age, 47 years [interquartile range, 25-65 years]) were included in this study. Gadolinium was detected in the CSF of all 68 patients in the gadobutrol group (100% [95% confidence interval: 94.7, 100]; range, 0.2-1494 ng/mL). CSF total protein level higher than 35 mg/dL and patient age of at least 18 years were associated with higher gadolinium concentrations (estimate: 1.1, with standard error [SE] of 0.26 [P < .001] and 0.91, with SE of 0.37 [P = .02], respectively). Conclusion Intravenous administration of the macrocyclic agent gadobutrol results in gadolinium accumulation within the CSF, even in the setting of normal renal function and no BBB dysfunction.