A Neural Circuit from Thalamic Paraventricular Nucleus to Central Amygdala for the Facilitation of Neuropathic Pain.

As one of the thalamic midline nuclei, the thalamic paraventricular nucleus (PVT) is considered to be an important signal integration site for many descending and ascending pathways that modulate a variety of behaviors, including feeding, emotions, and drug-seeking. A recent study has demonstrated that the PVT is implicated in the acute visceral pain response, but it is unclear whether the PVT plays a critical role in the central processing of chronic pain. Here, we report that the neurons in the posterior portion of the PVT (pPVT) and their downstream pathway are involved in descending nociceptive facilitation regarding the development of neuropathic pain conditions in male rats. Lesions or inhibition of pPVT neurons alleviated mechanical allodynia induced by spared nerve injury (SNI). The excitability of pPVT-central amygdala (CeA) projection neurons was significantly increased in SNI rats. Importantly, selective optogenetic activation of the pPVT-CeA pathway induced obvious mechanical hypersensitivity in naive rats. In addition, we used rabies virus (RV)-based and cell-type-specific retrograde transsynaptic tracing techniques to define a novel neuronal circuit in which glutamatergic neurons in the vlPAG were the target of the pPVT-CeA descending facilitation pathway. Our data suggest that this pPVTGlu+-CeA-vlPAGGlu+ circuit mediates central mechanisms of descending pain facilitation underlying persistent pain conditions.SIGNIFICANCE STATEMENT Studies have shown that the interactions between the posterior portion of the thalamic paraventricular nucleus (pPVT) and central amygdala (CeA) play a critical role in pain-related emotional regulation. However, most reports have associated this circuit with fear and anxiety behaviors. Here, an integrative approach of behavioral tests, electrophysiology, and immunohistochemistry was used to advance the novel concept that the pPVT-CeA pathway activation facilitates neuropathic pain processing. Using rabies virus (RV)-based and cell-type-specific retrograde transsynaptic tracing techniques, we found that glutamatergic neurons in the vlPAG were the target of the pPVT-CeA pathway. Thus, this study indicates the involvement of a pPVTGlu+-CeA-vlPAGGlu+ pathway in a descending facilitatory mechanism underlying neuropathic pain.

Enhanced thalamo-hippocampal synchronization during focal limbic seizures.

OBJECTIVE: The key factors that promote the termination of focal seizures have not been fully clarified. The buildup of neuronal synchronization during seizures has been proposed as one of the possible activity-dependent, self-limiting mechanisms. We investigate if increased thalamo-cortical coupling contributes to enhance synchronization during the late phase of focal seizure-like events (SLEs) generated in limbic regions. METHODS: Recordings were simultaneously performed in the nucleus reuniens of the thalamus, in the hippocampus and in the entorhinal cortex of the isolated guinea pig brain during focal bicuculline-induced SLEs with low voltage fast activity at onset. RESULTS: Spectral coherence and cross-correlation analysis demonstrated a progressive thalamo-cortical entrainment and synchronization in the generation of bursting activity that characterizes the final part of SLEs. The hippocampus is the first activated structure at the beginning of SLE bursting phase and thalamo-hippocampal synchronization is progressively enhanced as SLE develops. The thalamus takes the lead in generating the bursting discharge as SLE end approaches. SIGNIFICANCE: As suggested by clinical studies performed during pre-surgical intracranial monitoring, our data confirm a role of the midline thalamus in leading the synchronous bursting activity at the end of focal seizures in the mesial temporal regions.

Pathologic Findings and Clinical Course of Midline Paraventricular Gliomas Diagnosed Using a Neuroendoscope.

INTRODUCTION: Removal of midline paraventricular gliomas is difficult because of their deep localization and invasive character, requiring biopsy for pathologic diagnosis. This study aimed to assess the pathologic findings and clinical course of midline paraventricular gliomas diagnosed using a neuroendoscope. METHODS: This study was performed as a retrospective investigation using a neuroendoscope of 26 patients whose tumors were diagnosed as midline paraventricular gliomas. The main loci of the lesions were the thalamus (11 patients), tectum (6 patients), and other areas (9 patients). Of these 26 patients, 21 (81%) had accompanying obstructive hydrocephalus. Surgery was performed via the lateral ventricle using a flexible scope. For patients with obstructive hydrocephalus, we added endoscopic third ventriculostomy, septostomy, and/or plasty of the foramen of Monro. Pathologic diagnosis was determined according to hematoxylin-eosin staining and immunohistochemistry using anti-GFAP, anti-Ki-67, anti-H3-K27M, and anti-IDH1-R132H antibodies. RESULTS: The pathologic diagnoses were grade I (5 patients), grade II (3 patients), grade III (6 patients), and grade IV (4 patients) gliomas. Six patients were diagnosed as having high-grade glioma, which was difficult to distinguish between grade III and grade IV. Two patients were undiagnosable. H3-K27M was strongly positive in 8 of 15 patients with high-grade glioma. All patients with high-grade gliomas died or received best supportive care within 2 years after surgery. CONCLUSIONS: Neuroendoscopic surgery is useful for midline paraventricular gliomas in terms of the treatment of obstructive hydrocephalus, as well as pathologic diagnosis and genetic analysis, which are required under the World Health Organization 2016 classification.

Differential activation of c­Fos in the paraventricular nuclei of the hypothalamus and thalamus following myocardial infarction in rats.

Proto-oncogene c­Fos (c­Fos) is frequently used to detect a pathogenesis in central nervous system disorders. The present study examined changes in the immunoreactivity of c­Fos in the paraventricular nucleus of the hypothalamus (PVNH) and paraventricular nucleus of the thalamus (PVNT) following myocardial infarction (MI) in rats. Infarction in the left ventricle was examined by Masson's trichrome staining. Neuronal degeneration was monitored for 56 days after MI using crystal violet and Fluoro­Jade B histofluorescence staining. Changes in the immunoreactivity of c­Fos were determined using immunohistochemistry for c­Fos. The average infarct size of the left ventricle circumference was ~44% subsequent to MI. Neuronal degeneration was not detected in PVNH and PVNT following MI. c­Fos immunoreactive (+) cells were infrequently observed in the nuclei of the sham­group. However, the number of c­Fos+ cells was increased in the nuclei following MI and peaked in the PVNH and PVNT at 3 and 14 days, respectively. The number of c­Fos+ cells were comparable with the sham group at 56 days after MI. Therefore, MI may induce c­Fos immunoreactivity in PVNH and PVNT, this increase of c­Fos expression levels may be associated with the stress that occurs in the brain following MI.

Depression-like episodes in mice harboring mtDNA deletions in paraventricular thalamus.

Depression is a common debilitating human disease whose etiology has defied decades of research. A critical bottleneck is the difficulty in modeling depressive episodes in animals. Here, we show that a transgenic mouse with chronic forebrain expression of a dominant negative mutant of Polg1, a mitochondrial DNA (mtDNA) polymerase, exhibits lethargic behavioral changes, which are associated with emotional, vegetative and psychomotor disturbances, and response to antidepression drug treatment. The results suggested a symptomatic similarity between the lethargic behavioral change that was recurrently and spontaneously experienced by the mutant mice and major depressive episode as defined by DSM-5. A comprehensive screen of mutant brain revealed a hotspot for mtDNA deletions and mitochondrial dysfunction in the paraventricular thalamic nucleus (PVT) with similar defects observed in postmortem brains of patients with mitochondrial disease with mood symptoms. Remarkably, the genetic inhibition of PVT synaptic output by Cre-loxP-dependent expression of tetanus toxin triggered de novo depression-like episodes. These findings identify a novel preclinical mouse model and brain area for major depressive episodes with mitochondrial dysfunction as its cellular mechanism.

Excitatory amino acid transporter 2 downregulation correlates with thalamic neuronal death following kainic acid-induced status epilepticus in rat.

Recurrent seizures without interictal resumption (status epilepticus) have been reported to induce neuronal death in the midline thalamic region that has functional roles in memory and decision-making; however, the pathogenesis underlying status epilepticus-induced thalamic neuronal death is yet to be determined. We performed histological and immunohistochemical studies as well as cerebral blood flow measurement using 4.7 tesla magnetic resonance imaging spectrometer on midline thalamic region in Sprague-Dawley rats (n = 75, male, 7 weeks after birth, body weight 250-300 g) treated with intraperitoneal injection of kainic acid (10 mg/kg) to induce status epilepticus (n = 55) or normal saline solution (n = 20). Histological study using paraffin-embedded specimens revealed neuronal death showing ischemic-like changes and Fluoro-Jade C positivity with calcium deposition in the midline thalamic region of epileptic rats. The distribution of neuronal death was associated with focal loss of immunoreactivity for excitatory amino acid transporter 2 (EAAT2), stronger immunoreaction for glutamate and increase in number of Iba-1-positive microglial cells showing swollen cytoplasm and long processes. Double immunofluorescence study demonstrated co-expression of interleukin-1 beta (IL-1ß) and inducible nitric oxide synthase (iNOS) within microglial cells, and loss of EAAT2 immunoreactivity in reactive astrocytes. These microglial alterations and astrocytic EAAT2 downregulation were also observed in tissue without obvious neuronal death in kainic acid-treated rats. These results suggest the possible role of glutamate excitotoxicity in neuronal death in the midline thalamic region following kainic acid-induced status epilepticus due to astrocytic EAAT2 downregulation following microglial activation showing upregulation of IL-1ß and iNOS.

Damage to the dorsomedial thalamic nucleus, central lateral intralaminar thalamic nucleus, and midline thalamic nuclei on the right-side impair executive function and attention under conditions of high demand but not low demand.

This study reports a patient, OG, with a unilateral right-sided thalamic lesion. High resolution 3T magnetic resonance imaging revealed damage to the parvicellular and magnocellular subdivisions of the dorsomedial thalamus (DMT), the central lateral intralaminar nucleus (also known as the paralamellar DMT), the paraventricular and the central medial midline thalamic nuclei. According to the neuropsychological literature, the DMT, the midline and intralaminar thalamic nuclei influence a wide array of cognitive functions by virtue of their modulatory influences on executive function and attention, and this is particularly indicated under conditions of low arousal or high cognitive demand. We explored this prediction in OG, and compared his performance on a range of low and high demand versions of tests that tapped executive function and attention to a group of 6 age- and IQ-matched controls. OG, without exception, significantly under performed on the high-demand attention and executive function tasks, but performed normally on the low-demand versions. These findings extend and refine current understanding of the effects of thalamic lesion on attention and executive function.

Brain injury patterns in hypoglycemia in neonatal encephalopathy.

BACKGROUND AND PURPOSE: Low glucose values are often seen in term infants with NE, including HIE, yet the contribution of hypoglycemia to the pattern of neurologic injury remains unclear. We hypothesized that MR features of neonatal hypoglycemia could be detected, superimposed on the predominant HIE injury pattern. MATERIALS AND METHODS: Term neonates (n = 179) with NE were prospectively imaged with day-3 MR studies and had glucose data available for review. The predominant imaging pattern of HIE was recorded as watershed, basal ganglia, total, focal-multifocal, or no injury. Radiologic hypoglycemia was diagnosed on the basis of selective edema in the posterior white matter, pulvinar, and anterior medial thalamic nuclei. Clinical charts were reviewed for evidence of NE, HIE, and hypoglycemia (<46 mg/dL). RESULTS: The predominant pattern of HIE injury imaged included 17 watershed, 25 basal ganglia, 10 total, 42 focal-multifocal, and 85 cases of no injury. A radiologic diagnosis of hypoglycemia was made in 34 cases. Compared with laboratory-confirmed hypoglycemia, MR findings had a positive predictive value of 82% and negative predictive value of 78%. Sixty (34%) neonates had clinical hypoglycemia before MR imaging. Adjusting for 5-minute Apgar scores and umbilical artery pH with logistic regression, clinical hypoglycemia was associated with a 17.6-fold higher odds of MR imaging identification (P < .001). Selective posterior white matter and pulvinar edema were most predictive of clinical hypoglycemia, and no injury (36%) or a watershed (32%) pattern of injury was seen more often in severe hypoglycemia. CONCLUSIONS: In term infants with NE and hypoglycemia, specific imaging features for both hypoglycemia and hypoxia-ischemia can be identified.

Lesions of the thalamic reuniens cause impulsive but not compulsive responses.

On account of its strong efferent projections to the hippocampus, recent animal studies have emphasized an important role for the nucleus reuniens (NRe) of the midline thalamus in spatial memory. However, by virtue of its reciprocal connections with the orbital and ventromedial prefrontal cortex, the NRe may also be involved in aspects of executive inhibition. To date, there has been no systematic attempt to examine the role of the NRe in inhibitory mechanisms of response control. Accordingly, we compared rats with neurotoxic lesions of the NRe with sham surgery controls on performance of the 5-choice reaction time task, a test of visuospatial attention and inhibitory control. When tested post-operatively, rats with NRe lesions were unable to actively inhibit premature responses when the intertrial interval was varied. However, the same rats with NRe lesions showed normal inhibition of perseverative responses, and under some conditions were less perseverative than shams. The NRe lesion was also associated with a reduction in omissions and fast reward collection latencies, which persisted 2 months following surgery. The NRe lesion did not affect response accuracy or latency to respond correctly throughout the course of experimental testing. Together, these results signify the important role of the NRe in impulse inhibition, especially when slight changes are made to the temporal demands of the environment, and reveal the potential contribution of the NRe in motivational processes.

Neonatal exposure to genistein adversely impacts the ontogeny of hypothalamic kisspeptin signaling pathways and ovarian development in the peripubertal female rat.

Neonatal exposure to estrogenic endocrine disrupting compounds (EDCs) can advance pubertal onset and induce premature anestrous in female rats. It was recently discovered that hypothalamic kisspeptin (KISS) signaling pathways are sexually dimorphic and regulate both the timing of pubertal onset and estrous cyclicity. Thus we hypothesized that disrupted sex specific ontogeny of KISS signaling pathways might be a mechanism underlying these EDC effects. We first established the sex specific development of KISS gene expression, cell number and neural fiber density across peripuberty in the anteroventral periventricular nucleus (AVPV) and arcuate nucleus (ARC), hypothesizing that the sexually dimorphic aspects of KISS signaling would be most vulnerable to EDCs. We next exposed female rats to the phytoestrogen genistein (GEN, 1 or 10 mg/kg bw), estradiol benzoate (EB, 10 µg), or vehicle from post natal day (P) 0-3 via subcutaneous (sc) injection. Animals were sacrificed on either P21, 24, 28, or 33 (n=5-14 per group at each age). Vaginal opening was significantly advanced by EB and the higher dose of GEN compared to control animals and was accompanied by lower numbers of KISS immunoreactive fibers in the AVPV and ARC. Ovarian morphology was also assessed in all age groups for the presence of multiple oocyte follicles (MOFs). The number of MOFs decreased over time in each group, and none were observed in control animals by P24. MOFs were still present, however, in the EB and 10 mg/kg GEN groups beyond P24 indicating a disruption in the timing of ovarian development.

The participation of a neurocircuit from the paraventricular thalamus to amygdala in the depressive like behavior.

Depression is a neuropsychological disease derived from genetic, biochemical, environmental, and psychological factors. However the neurocircuits involved in it are not clear. We introduced the forced swimming test (FST) as a model of the depressive like behavior. In our study, the participation of projections from paraventricular nucleus of the thalamus (PVT) in FST was detected. The retrograde tracing combined with immunofluorescent detection of c-fos was used. Our results showed that the FST greatly increased the c-fos level in PVT and the central amygdale (CE) neurons. These populations of activated neurons in the PVT and the CE were also labeled by the retrograde tracer FG injected in the CE, suggesting that the activation of PVT was involved in this depressive like behavior by relaying information to the CE.

The targets of acetone cyanohydrin neurotoxicity in the rat are not the ones expected in an animal model of konzo.

Konzo is a neurotoxic motor disease caused by excess consumption of insufficiently processed cassava. Cassava contains the cyanogenic glucoside linamarin, but konzo does not present the known pathological effects of cyanide. We hypothesized that the aglycone of linamarin, acetone cyanohydrin, may be the cause of konzo. This nitrile rapidly decomposes into cyanide and acetone, but the particular exposure and nutrition conditions involved in the emergence of konzo may favor its stabilization and subsequent acute neurotoxicity. A number of preliminary observations were used to design an experiment to test this hypothesis. In the experiment, young female Long-Evans rats were given 10mM acetone cyanohydrin in drinking water for 2 weeks, and then 20mM for 6 weeks. Nutrition deficits associated with konzo were modeled by providing tapioca (cassava starch) as food for the last 3 of these weeks. After this period, rats were fasted for 24h in order to increase endogenous acetone synthesis, and then exposed to 0 (control group) or 50 micromol/kg-h of acetone cyanohydrin for 24h (treated group) through subcutaneous osmotic minipump infusion (n=6/group). Motor activity and gait were evaluated before exposure (pre-test), and 1 and 6 days after exposure. Brains (n=4) were stained for neuronal degeneration by fluoro-jade B. Rats exposed to 50 micromol/kg-h of acetone cyanohydrin showed acute signs of toxicity, but no persistent motor deficits. Two animals showed fluoro-jade staining in discrete thalamic nuclei, including the paraventricular and the ventral reuniens nuclei; one also exhibited labeling of the dorsal endopiriform nucleus. Similar effects were not elicited by equimolar KCN exposure. Therefore, acetone cyanohydrin may cause selective neuronal degeneration in the rat, but the affected areas are not those expected in an animal model of konzo.

Neurotoxic lesions of the thalamic reuniens or mediodorsal nucleus in rats affect non-mnemonic aspects of watermaze learning.

Rats with bilateral neurotoxic reuniens (RE), mediodorsal (MD), hippocampal (HIPP) or sham (SH) lesions were tested in a standard watermaze task, together with unoperated rats. RE-rats and SH-controls readily learned to swim directly to a hidden platform. In contrast, MD-rats displayed a transient deficit characterized initially by thigmotaxis. Like in previous studies, HIPP-rats had long latencies throughout training and displayed more random swims than the other groups. In a memory probe test with the platform removed, SH- and RE-rats approached the correct location relatively directly but, whereas SH-controls persistently searched in the training quadrant, RE-rats switched to searching all over the pool. The MD-group swam in loops to the platform, but then displayed persistent searching in the training quadrant. The HIPP-group performed at chance. These distinct patterns indicate that, although their search strategies were different, RE- and MD-rats had acquired sufficient knowledge about the platform location and could recall information in the probe test. All groups performed well in a subsequent cue test with a visible platform, with RE-rats initially escaping faster than the SH- and HIPP-groups, and MD-rats improving from an initially poorer level of performance to control level. This indicates that there were no sensorimotor or motivational deficits associated with any of the lesions. In conclusion, while the RE and MD nuclei seem not to be critical for the learning and memory of a standard watermaze task, they may contribute to non-mnemonic strategy shifting when animals are challenged in ways that do not occur during training.

Changes in midline thalamic recruiting responses in the prefrontal cortex of the rat during the development of chronic limbic seizures.

PURPOSE: Mesial temporal lobe epilepsy (MTLE) is a common form of epilepsy that affects the limbic system and is associated with decreases in memory and cognitive performance. The medial prefrontal cortex (PC) in rats, which has a role in memory, is associated with and linked anatomically to the limbic system, but it is unknown if and how MTLE affects the PC. METHODS: We evoked responses in vivo in the PC by electrical stimulation of the mediodorsal (MD) and reuniens (RE) nuclei of the thalamus at several time points following status epilepticus, before and after onset of spontaneous seizures. Kindled animals were used as additional controls for the effect of seizures that were independent of epilepsy. RESULTS: Epileptic animals had decreased response amplitudes and significantly reduced recruiting compared to controls, whereas kindled animals showed an increase in both measures. These changes were not associated with neuronal loss in the PC, although there was significant loss in both the MD and RE in the epileptic animals. CONCLUSIONS: There is a significant reduction in the thalamically induced evoked responses in the PCs of epileptic animals. This finding suggests that physiologic dysfunction in MTLE extends beyond primary limbic circuits into areas without overt neuronal injury.

Skew deviation as the initial manifestation of left paramedian thalamic infarction.

We describe a 73-year-old man who developed diplopia as the initial manifestation of a left thalamic infarction. By the time he reached the emergency department, clouded consciousness precluded localization of the lesion. Results of brain MRI were initially interpreted as negative. Ophthalmologic examination several hours later disclosed a small vertical ocular misalignment attributed to skew deviation. This finding led to careful scrutiny of the upper brainstem on MRI. Comparison of the diffusion, apparent diffusion coefficient, and exponential apparent diffusion coefficient MRI studies allowed a diagnosis of subtle left thalamic infarction. The recognition of skew deviation in this setting is important because it may be the most specific indicator of a brainstem lesion.

Analysis of the actions of nucleus reuniens and the entorhinal cortex on EEG and evoked population behavior of the hippocampus.

Although the hippocampal theta rhythm is thought to be linked to memory processes, its mechanism of action is unknown. Furthermore, the hippocampus forms strong connections with a functionally similar structure, the medial prefrontal cortex (mPFC). The midline thalamus appears to be an intermediate between these two structures. We recorded neurons of a midline nucleus (nucleus reuniens, RE) during theta and non-theta states. Additionally, we recorded hippocampal CA1 population responses to RE stimulation. RE cell firing patterns are classified as (i) spike rate response to stimulation (ii) determination of bursting events (iii) coherence estimation between hippocampal EEG and RE response to stimulation (within the theta frequency band of 5 - 12 Hz). The present data suggests an increase in RE spike rate due to tail pinch elicited theta activity, with no evidence of bursting activity and a weak coherence within the theta band. Furthermore, we evaluated evoked excitatory post-synaptic potentials (EPSPs) in the hippocampal CA1 to RE stimulation, as well as entorhinal cortex (EC) stimulation. We demonstrated a consistent reduction in evoked potential (EP) latency at CA1 to RE and EC stimulation during theta compared to non-theta states.

Severe reversible toxic encephalopathy induced by cisplatin in a patient with cervical carcinoma receiving combined radiochemotherapy.

CASE REPORT: A 45-year-old patient with cervix carcinoma received combined radiochemotherapy including cisplatin. After a cumulative dose of 240 mg/m(2) the patient suddenly became somnolent and developed a severe tetraparesis and generalized seizures. After ruling out intracranial bleeding, cerebral metastases as well as infectious and metabolic causes of this condition, a severe toxic encephalopathy was diagnosed based on the clinical findings and MRI scans. After symptomatic treatment on the intensive care unit all symptoms were completely reversible. CONCLUSION: Toxic encephalopathy is a rare but dramatic complication of various cytostatic drugs. With the widespread use of cisplatin this rare disorder should be kept in mind.

Alterations in GABA(A) receptor mediated inhibition in adjacent dorsal midline thalamic nuclei in a rat model of chronic limbic epilepsy.

There is evidence that the dorsal midline thalamus is involved in the seizures of limbic epilepsy. However, little is known about the inhibitory synaptic function in this region. In the present study, inhibitory postsynaptic currents (IPSCs) mediated by GABA(A) receptors were recorded from the mediodorsal (MD) and paraventricular (PV) nuclei from control and epileptic animals. In the MD, the spontaneous (s)IPSCs for epileptic animals had a lower frequency, prolonged rise time, prolonged decay, but unaltered net charge transfer compared with controls. The miniature (m)IPSC parameters were unaltered in the epileptic animals. In contrast, in the PV, both sIPSCs and mIPSCs in the epileptic animals were more frequent with larger amplitudes and there was an increase in the net charge transfer compared with controls. The rise times of the sIPSCs of the PV neurons were significantly prolonged, whereas the weighted decay time of the mIPSC was significantly shortened in epileptic animals. These findings suggest that the changes associated with inhibitory synaptic transmission in limbic epilepsy are not uniform across regions in the thalamus that are part of the seizure circuit.

Double inversion recovery brain imaging at 3T: diagnostic value in the detection of multiple sclerosis lesions.

BACKGROUND AND PURPOSE: To prospectively determine the sensitivity in the detection of multiple sclerosis (MS) lesions by using double inversion recovery (DIR), fluid-attenuated inversion recovery (FLAIR), and T2-weighted turbo spin-echo (T2 TSE) MR imaging at 3T. METHODS: Seventeen patients presenting with a clinically isolated syndrome (CIS) suggestive of MS, 9 patients with definite MS, and 6 healthy control subjects were included. Imaging was performed on a 3T MR system using DIR, FLAIR, and T2 TSE sequences. Lesions were counted and classified according to 5 anatomic regions: infratentorial, periventricular, deep white matter, juxtacortical, and mixed white matter-gray matter. The sensitivity at DIR was compared with the corresponding sensitivity at FLAIR and T2 TSE sequence. The contrast between lesions and normal-appearing gray matter, normal-appearing white matter, and CSF was determined for all sequences. RESULTS: Because of higher lesion-white matter contrast, the DIR showed a higher number of lesions compared with the FLAIR (7% gain, P = 0.04) and the T2 TSE (15% gain, P = 0.01). The higher sensitivity was also significant for the infratentorial region compared with the FLAIR (56% gain, P = 0.02) and the T2 TSE (44% gain, P = 0.02). Compared with the FLAIR, no significant changes of the lesion load measurements were observed in the supratentorial brain: slightly higher numbers of periventricular and mixed gray matter-white matter lesions on the DIR were counterbalanced by a slightly reduced sensitivity regarding juxtacortical lesions. CONCLUSION: DIR brain imaging at 3T provides the highest sensitivity in the detection of MS lesions especially in the infratentorial region.