Brain abnormalities in bipolar disorder detected by quantitative T1ρ mapping

Abstract

Abnormal metabolism has been reported in bipolar disorder, however these studies have been limited to specific regions of the brain. To investigate whole-brain changes potentially associated with these processes, we applied a magnetic resonance imaging technique novel to psychiatric research, quantitative mapping of T1 relaxation in the rotating frame (T1ρ). This method is sensitive to proton chemical exchange, which is affected by pH, metabolite concentrations, and cellular density with high spatial resolution relative to alternative techniques such as magnetic resonance spectroscopy and positron emission tomography. Study participants included 15 patients with bipolar I disorder in the euthymic state and 25 normal controls balanced for age and gender. T1ρ maps were generated and compared between the bipolar and control groups using voxel-wise and regional analyses. T1ρ values were found to be elevated in the cerebral white matter and cerebellum in the bipolar group. However, volumes of these areas were normal as measured by high-resolution T1- and T2-weighted magnetic resonance imaging. Interestingly, the cerebellar T1ρ abnormalities were normalized in participants receiving lithium treatment. These findings are consistent with metabolic or microstructural abnormalities in bipolar disorder and draw attention to roles of the cerebral white matter and cerebellum. This study highlights the potential utility of high-resolution T1ρ mapping in psychiatric research.

Multivariate characterization of white matter heterogeneity in autism spectrum disorder

“…Standardized scores of head circumference, brain volume, and other brain features have been routinely used to assess the distribution of brain characteristics in individuals with ASD (Barnea-Goraly et al, 2004, Courchesne et al, 2003, Herbert et al, 2004, Lainhart et al, 2006, Lainhart et al, 1997, Miles et al, 2000, Prigge et al, 2013), as well as other disorders, including mild traumatic brain injury (Kim et al, 2013, Lipton et al, 2012), bipolar disorder (Johnson et al, 2015), multiple sclerosis (Poonawalla et al, 2010), and Alzheimer's disease (Matsuda, 2014), among others. However, as it becomes commonplace to acquire multi-modal information from study participants, it becomes necessary to account for the multidimensional aspects of data.…”

Aberrant Cerebellar Connectivity in Bipolar Disorder With Psychosis

“…Indeed, a growing body of evidence points to clinical (5–14), molecular (15–19), neurochemical (20–22), structural (23–39), and functional (40–44) abnormalities of the cerebellum in BP. The cerebellum is reciprocally connected to higher-level association areas in prefrontal (45) and posterior parietal (46) cortices and limbic regions in medial temporal lobe (47–49), and cerebellar dysfunction may mirror or contribute to well-established dysfunctions of these higher-level association areas in BP.…”

Relationship altered between functional T1ρ and BOLD signals in bipolar disorder

“…The absence of group differences in these areas may be explained by the fact that the flashing checkerboard task does not directly interrogate these networks, however, the altered coupling between BOLD and fT1ρ suggests that dysfunction may be present in these regions even when they are not specifically activated by a task. For example, through the accumulation of metabolites that fT1ρ is sensitive to, but that are relatively independent from neuronal activation in bipolar disorder, which may be related to group differences in quantitative T1ρ found in previous work by our group in this population (Johnson et al., 2015a). …”

“…MR spectroscopy studies have shown that baseline pH is reduced (i.e., more acidic) in the anterior cingulate in people with bipolar disorder in the euthymic state compared to normal controls (Kato, Kunugi, Nanko, & Kato, 2000; Kato et al., 1998). Furthermore, a recent study using static, whole‐brain, high‐resolution quantitative T1ρ mapping detected elevated T1ρ relaxation times in the cerebellum and cerebral white matter consistent with reduced basal pH in the euthymic state of people with bipolar disorder compared to healthy controls (Johnson et al., 2015a; Johnson et al., 2015b). These baseline differences in pH and metabolic state may therefore result in differences in functional activity.…”