تفاوت پرفیوژن مغزی در زنان حاضر با/بهبود بیماری بی اشتهایی عصبی

Anorexia nervosa is a serious psychiatric disorder characterized by restricted eating, a pursuit of thinness, and altered perceptions of body shape and size. Neuroimaging in anorexia nervosa has revealed morphological and functional alterations in the brain. A better understanding of physiological changes in anorexia nervosa could provide a brain-specific health marker relevant to treatment and outcomes. In this study, we applied several advanced magnetic resonance imaging (MRI) techniques to quantify regional and global cerebral blood flow (CBF) in 25 healthy women (HC), 23 patients currently with anorexia (AN-C) and 19 patients in long-term weight recovery following anorexia (AN-WR). Specifically, CBF was measured with pseudo-continuous arterial spin labeling (pCASL) MRI and then verified by a different technique, phase contrast (PC) MRI. Venous T2 values were determined by T2 relaxation under spin tagging (TRUST) MRI, and were used to corroborate the CBF results. These novel techniques were implemented on a standard 3T MRI scanner without any exogenous tracers, and the total scan duration was less than 10 min. Voxel-wise comparison revealed that the AN-WR group showed lower CBF in bilateral temporal and frontal lobes than the AN-C group. Compared with the HC group, the AN-C group also showed higher CBF in the right temporal lobe. Whole-brain-averaged CBF was significantly decreased in the AN-WR group compared with the AN-C group, consistent with the PC-MRI results. Venous T2 values were lower in the AN-WR group than in the AN-C group, consistent with the CBF results. A review of prior work examining CBF in anorexia nervosa is included in the discussion. This study identifies several differences in the cerebral physiological alterations in anorexia nervosa, and finds specific differences relevant to the current state of the disorder.

Anorexia nervosa is a serious psychiatric disorder characterized by calorie restriction leading to significant weight loss, fear of weight gain, and a disturbance in body-image (American Psychiatric Association, 1994). The precise etiology of anorexia nervosa is still unknown, but many factors are thought to contribute to anorexia, including genetic, neural, psychological, and social (Garfinkel and Garner, 1983, Bulik et al., 2008, Kaye et al., 2011, Brown and Keel, 2012 and Scott-Van Zeeland et al., 2014). Unfortunately, the success of treatments is very limited, with nearly 5% of patients dying from the disorder, the highest mortality rate for any mental illness (Hoek, 2006 and Bulik et al., 2008). A better understanding of the physiological characteristics of brain function in anorexia nervosa may assist in understanding both the causes and consequences of the illness. Cerebral microvasculature abnormalities may play a significant role in the psychiatric disorders (West, 2007). It is plausible that abnormalities in microvasculature can result in functional deficits because of the coupling between neuronal activity and blood oxygen consumption (Roy and Sherrington, 1890 and Kuschinsky, 1991). The most common techniques used to detect this abnormality are to measure brain perfusion and metabolic parameters by nuclear medicine techniques such as positron emission tomography (PET) and single-photon emission computed tomography (SPECT). Techniques based on magnetic resonance imaging (MRI) are more attractive for psychiatric research because they provide both noninvasive and reproducible measures of cerebral microvasculature (Theberge, 2008). Several studies have shown agreement between MRI-based physiological studies and nuclear medicine studies (Liu et al., 2012 and Zimny et al., 2015). Arterial spin labeling (ASL) MRI relies on the use of magnetically tagged or labeled blood as an endogenous tracer that does not involve any injection of MRI contrast agent, making it more convenient for subjects. In recent years, it has been used to study several psychiatric diseases, such as schizophrenia (Risterucci et al., 2005 and Ota et al., 2014), depression (Doraiswamy et al., 1999, Clark et al., 2001, Clark et al., 2006a and Clark et al., 2006b), dementia (Du et al., 2006 and Hayasaka et al., 2006), and addictions (Gazdzinski et al., 2006 and Clark et al., 2007). Anorexia nervosa is associated both with medical complications (Garfinkel and Garner, 1983 and Michell and Crow, 2006) and disturbances of brain function (Bailer and Kaye, 2011 and Kaye et al., 2011). As such, cerebral vasculature changes may be particularly important in anorexia nervosa, and cerebral blood flow (CBF) might provide a measure of the severity of brain dysfunction occurring in patients with anorexia. Physiological brain differences in anorexia nervosa have been investigated in studies using nuclear medicine-based techniques, with largely heterogeneous results (Gordon et al., 1997, Kuruoglu et al., 1998, Naruo et al., 2001, Råstam et al., 2001, Takano et al., 2001, Chowdhury et al., 2003, Kojima et al., 2005, Lask et al., 2005, Key et al., 2006, Matsumoto et al., 2006, Frank et al., 2007, Yonezawa et al., 2008, Komatsu et al., 2010 and Frampton et al., 2011). A review of this literature is included in the discussion and summarized in Table 1. Table 1. Prior studies examining regional cerebral blood flow (rCBF) in patients with anorexia nervosa (AN) in chronological order of publication. Technique Experimental design Results Gordon et al., 1997 99mTc HMPAO/ECD SPECT rCBF measured at one time point for AN pediatric patients (n, 15, age, 13.1, weight for height, 82%). 13 or 15 patients with unilateral reduced rCBF in temporal lobe. Follow-up scans with same pattern. Kuruoglu et al., 1998 99mTc HMPAO SPECT Case-reports of two subjects with AN, aged 16 and 18. Both subjects scanned initially, treated for over a year, rescanned after 3 months of normalized weight. Bilateral frontal, parietal, and frontotemporal hypoperfusion at low weight, normal after treatment. Takano et al., 2001 123I –IMP SPECT rCBF compared at one time point for 2 groups: HC (n, 8, age 28.3, BMI, 19.7) and AN (n, 14, age, 21, BMI, 14.0). Patients with hypoperfusion in medial prefrontal cortex (MPFC) and anterior cingulate (ACC) and hyperperfusion of thalamus and amygdala-hippocampus. Naruo et al.,2001 PAO SPECT rCBF compared at one time point for 3 groups: HC (n, 7, age, 21.9, BMI, 20.0), AN-R a (n, 7, age, 21.7, BMI, 12.8), and AN-BP b (n, 7, age, 25.6, BMI, 14.5). Reduced rCBF in bilateral ACC and frontal regions in AN-R group relative to AN-BP and HC groups. Råstam et al., 2001 99mTc HMPAO SPECT rCBF compared for AN (n, 21, age 22.1, BMI, 21.2) and non-psychiatric pediatric patients (n, 9, age 9.7, BMI, 16.2). Subjects with AN included both weight-recovered and underweight. AN group with hypoperfusion of temporal, parietal, occipital, and orbitofrontal lobes. Chowdhury et al., 2003 99mTc ECD SPECT rCBF measured at one time point for 15 new-onset pediatric subjects with AN (n, 15, age, 14.9, weight for height, 83%). 73% of patients with unilateral hypoperfusion of one region (9 with temporal lobe, 5 with parietal lobe, and 3 with frontal lobe and thalamux) Lask et al., 2005 99mTc ECD SPECT rCBF measured at one time point for pediatric subjects with AN (n, 24, age, 14.4, BMI, not reported) 66% of patients with unilateral hypoperfusion in different regions (12, temporal; 4 parietal; 5 thalamic) Kojima et al., 2005 99mTc HMPAO SPECT rCBF measured before and after weight recovery for subjects with AN-R (n, 12, age 18, BMI before treatment, 12.5, BMI after treatment, 15.6, length of treatment, 104 days) and compared to HC measured only once (n, 11, age, 22, BMI, 20.1). Before treatment, AN-R group with lower rCBF in ACC, right parietal, insula, occipital lobes. After weight gain, rCBF increased in right parietal with decreased in basal ganglia and cerebellum Key et al., 2006 99mTc ECD SPECT rCBF compared at one time point for 2 groups of adult women: HC (n, 11, age, 26, BMI, 22), and AN (n, 11, age, 28, BMI, 17). 8 of 11 patients with hypoperfusion in the anterior temporal lobe and/or caudate nuclei Matsumoto et al., 2006 123I –IMP SPECT rCBF examined before and after weight recovery: AN only (n, 8, age, 18.5, BMI at admission, 12.9, at discharge, 18.8, length of treatment 175 days). After treatment, rCBF increased in precuneus, ACC, posterior cingulate gyrus (PCG), right dorsolateral prefrontal (DLPFC), and MPFC. Frank et al., 2007 [15O] water PET rCBF compared at one time point for 3 groups: HC (n, 8, age, 26, BMI, 23), weight-recovered AN-R (n, 10, age, 24, BMI, 24), and weight-recovered AN-BP (n, 8, age, 24, BMI, 25). rCBF similar across groups. Yonezawa et al., 2008 99mTc HMPAO SPECT rCBF compared at one time point for 3 groups: HC (n, 10, age, 20.6, BMI, 19.7), AN-R (n, 13, age, 22.2, BMI, 13.8), and AN-BP (n, 13, age, 22.3, BMI, 13.4) Both AN-R and AN-BP with decreased perfusion in bilateral subcallosal gyrus, PCG, corpus callosum, midbrain, and pons. Komatsu et al., 2010 123I –IMP SPECT rCBF compared before and after weight recovery for pediatric AN (n=10, age 13.2 yrs, initial BMI 13.1, post-treatment BMI 16.6, treatment 4 months). Following treatment, increased rCBF in bilateral parietal lobe, and right PCG. Frampton et al., 2011 99mTc ECD SPECT Follow-up of 9 AN participants now in weight-recovery ~4 years after scans for the Chowdhury, 2003 study. 7 patients with significant and persisting unilateral temporal hypoperfusion. a AN-R: anorexia nervosa, restricting type. b AN-BP: anorexia nervosa, binge-purge type. Table options Here, we applied pseudo-continuous arterial spin labeling (pCASL) as well as other advanced MRI techniques to obtain rapid, non-invasive measures of cerebral physiological parameters, including CBF and venous T2 values, markers of blood oxygenation. Further, we compared these parameters among subjects with a current diagnosis of anorexia nervosa (AN-C), subjects in long-term weight recovery from anorexia nervosa (AN-WR), and healthy women (HC) to determine if cerebral physiological characteristics differed during different stages of the disorder.

The present study used two different non-invasive techniques to assess CBF. Findings suggest patients in long-term recovery from anorexia, compared with currently ill patients, have lower CBF values. These differences in CBF occurred primarily in temporal and frontal lobes in the AN-C and AN-WR comparison. In addition, TRUST MRI revealed lower venous T2 values in AN-WR patients, further supporting the CBF findings. The AN-C cohort also showed elevated CBF compared with the HC cohort in the right temporal lobe. These data support the idea that alterations in the cerebral physiology are present in anorexia, and further suggest that localized differences may be present in the temporal and frontal lobes. Future studies should focus on development of a mechanistic and functional understanding of the consequences of these CBF alterations.