Lateralized abnormality of high energy phosphate metabolism in the frontal lobes of patients with bipolar disorder detected by phase-encoded<sup>31</sup>P-MRS

Kato, Takeshi; Shioiri, Toshiki; Murashita, Jun; Hamakawa, Hiroshi; Takahashi, Yasuji; Inubushi, Toshiro; Takahashi, Saburo

doi:10.1017/s003329170003347x

Cited by 115 publications

(92 citation statements)

References 34 publications

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“…[4] we see that gain is largest when T 1 Ͼ TR. Additionally, by setting dGain/d␣ ϭ 0 and solving for ␣, we find that gain is maximized when …”

Section: Lfa Methodsmentioning

confidence: 68%

“…Since studies at 1.5T and 2T have shown that bipolar subjects have decreased membrane phospholipid precursor levels in their temporal (2) and frontal lobes (3), and a deficit of high-energy phosphates in their frontal lobes (4), as compared to normal subjects, the development of a quantitative technique that evaluates these particular metabolites is crucial for diagnosis. However, 31 P MR spectroscopy (MRS) quantitative techniques are confounded by low signal-to-noise ratio (SNR) and poor spatial resolution.…”

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confidence: 99%

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Selective maximization of ³¹P MR spectroscopic signals of in vivo human brain metabolites at 3T

Blenman

Port

Felmlee

2007

Magnetic Resonance Imaging

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Purpose: To develop a short TR, short TE, large flip angle (LFA), in vivo 31 P MR spectroscopy (MRS) technique at 3T that selectively maximizes the signal-to-noise ratio (SNR) of long T 1 human brain metabolites implicated in bipolar disorder. Materials and Methods:Two pulse sequences were evaluated for efficiency. Slice profiles acquired with the scaled, sinc-shaped, radiofrequency (RF) LFA pulses were compared to those acquired with Shinnar-Le Roux (SLR) RF LFA pulses. The SLR-based LFA pulse sequence was used to maximize the inorganic phosphate signal in a phantom, after which volunteer metabolite signals were selectively maximized and compared to their correlates acquired with conventional spin-echo methods. Results:The comparison of slice profiles acquired with sinc-shaped RF LFA pulses vs. SLR RF LFA pulses showed that SLR-based pulse sequences, with their improved excitation and slice profiles, yield significantly better results. In vivo LFA spin-echo MRS implemented with SLR pulses selectively increased the 31 P MRS signal, by as much as 93%, of human brain metabolites that have T 1 times longer than the TR of the acquisition. Conclusion:The data show that the LFA technique can be employed in vivo to maximize the signal of long T 1 31 P brain metabolites at a given TE and TR. LFAs ranging between 120°and 150°are shown to maximize the 31 P signal of human brain metabolites at 3T. OVER THE PAST DECADE, the 31 P nucleus has been used to study bipolar disorder-a neuropsychiatric disease that can be difficult to diagnose and affects about three million Americans over their lifetime (1). Since studies at 1.5T and 2T have shown that bipolar subjects have decreased membrane phospholipid precursor levels in their temporal (2) and frontal lobes (3), and a deficit of high-energy phosphates in their frontal lobes (4), as compared to normal subjects, the development of a quantitative technique that evaluates these particular metabolites is crucial for diagnosis. However, 31 P MR spectroscopy (MRS) quantitative techniques are confounded by low signal-to-noise ratio (SNR) and poor spatial resolution. These problems result from the inherently low sensitivity of 31 P nuclei and the long T 1 times of the metabolites, which necessitate long data acquisition times. Additionally, the low brain metabolite concentrations, as well as the short T 2 relaxation times of the 31 P metabolites, contribute to the low SNR of 31 P MRS. To address these issues, our approach was to develop a clinically feasible large flip angle (LFA) spin-echo technique at 3 T that maximizes the SNR of relevant metabolites.An increase in the field strength from 1.5T to 3T is expected to yield a two-fold gain in SNR with better spectral separation. T 1 relaxation values of 31 P brain metabolites range from 0.6 to 3 seconds (5,6) at 1.5T, and since T 1 s typically lengthen as field strength increases, the LFA technique should be very useful at the increased field strength of 3T. LFA 1 H spin-echo imaging has been shown to selectively increase the signal of ...

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“…[4] we see that gain is largest when T 1 Ͼ TR. Additionally, by setting dGain/d␣ ϭ 0 and solving for ␣, we find that gain is maximized when …”

Section: Lfa Methodsmentioning

confidence: 68%

mentioning

confidence: 99%

Selective maximization of ³¹P MR spectroscopic signals of in vivo human brain metabolites at 3T

Blenman

Port

Felmlee

2007

Magnetic Resonance Imaging

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“…31 Together, these studies add neurochemical support to the contention that mood disorders are associated with regional neuronal loss and/or reductions in neuronal viability/function. There have also been a number of reports of abnormal brain high energy phosphate metabolism in mood disorder patients, most notably decreased phosphocreatine (PCr) and/or ATP levels, [32][33][34][35][36][37][38] as well as abnormal phospholipid metabolism (predominantly phosphomonoesters and phosphodiesters). 33,34,36,37,39,40 The most extensive series of studies investigating possible abnormalities in brain energy regulation in mood disorders have been conducted by Kato and associates.…”

Section: Volumetric Brain Imagingmentioning

confidence: 99%

Neuroplasticity and cellular resilience in mood disorders

et al. 2000

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Although mood disorders have traditionally been regarded as good prognosis diseases, a growing body of data suggests that the long-term outcome for many patients is often much less favorable than previously thought. Recent morphometric studies have been investigating potential structural brain changes in mood disorders, and there is now evidence from a variety of sources demonstrating significant reductions in regional CNS volume, as well as regional reductions in the numbers and/or sizes of glia and neurons. Furthermore, results from recent clinical and preclinical studies investigating the molecular and cellular targets of mood stabilizers and antidepressants suggest that a reconceptualization about the pathophysiology and optimal long-term treatment of recurrent mood disorders may be warranted. It is proposed that impairments of neuroplasticity and cellular resilience may underlie the pathophysiology of mood disorders, and further that optimal long-term treatment for these severe illnesses may only be achieved by the early and aggressive use of agents with neurotrophic/ neuroprotective effects. It is noteworthy that lithium, valproate and antidepressants indirectly regulate a number of factors involved in cell survival pathways including CREB, BDNF, bcl-2 and MAP kinases, and may thus bring about some of their delayed long-term beneficial effects via underappreciated neurotrophic effects. The development of novel treatments which more directly target molecules involved in critical CNS cell survival and cell death pathways have the potential to enhance neuroplasticity and cellular resilience, and thereby modulate the long-term course and trajectory of these devastating illnesses. Molecular Psychiatry (2000) 5, 578-593.Keywords: atrophy; cell death; neuroprotection; lithium; bcl-2; MAP kinase; neurite; neurotrophic; neurogenesis; N-acetylaspartate; gray matter There is mounting evidence that recurrent mood disorders-once considered 'good prognosis diseases'-are, in fact, often very severe and life-threatening illnesses. Recurrent mood disorders can have devastating long-term effects, and the cost of these illnesses in terms of human suffering, productivity and health care is enormous. Suicide is the cause of death in 10-20% of individuals, and in addition to suicide, mood disorders are associated with many other deleterious health-related effects. 1-5 Indeed, a recent study which controlled for physical illness, smoking and alcohol consumption found that the magnitude of the increased mortality risk conferred by the presence of high depressive symptoms was similar to that of stroke and congestive heart failure. 5 Not surprisingly, the costs associated with disability and premature death represent an economic burden of tens of billions of dollars annually in the United States alone. 1,6,7 It is now recognized that, for many patients, the long-term outCorrespondence: HK Manji, MD,

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“…Most information about PI metabolism in BPD derives from studies using tissues other than CNS (Atack et al 1995;Feldman et al 1997). Indirect evidence for altered PI metabolism in individuals with BPD has been suggested by a reduction in cytosolic and membrane-associated PKC activities in platelets of lithium-treated subjects with BPD (Friedman et al 1993); and by elevated platelet membrane phosphatidylinositol-4,5-bisphosphate (PIP2) in medication-free patients with BPD during the manic phase (Brown et al 1993).Indirect in vivo measurement of brain inositol metabolism in adult patients treated with lithium has been attempted through measuring phosphomonoester peaks with phosphorus ( 31 P) magnetic resonance spectroscopy (MRS) (Kato et al 1995), proton ( 1 H) MRS (Kato et al 1996;Silverstone et al 1996) and lithium MRS (Gonzalez et al 1993;Kato et al 1993;Sachs et al 1995) (involving a lithium-sensitive coil). In vivo 1 H MRS is a non-invasive technique for measuring metabolite concentrations in living tissue .…”

mentioning

confidence: 99%

“…Indirect in vivo measurement of brain inositol metabolism in adult patients treated with lithium has been attempted through measuring phosphomonoester peaks with phosphorus ( 31 P) magnetic resonance spectroscopy (MRS) (Kato et al 1995), proton ( 1 H) MRS (Kato et al 1996;Silverstone et al 1996) and lithium MRS (Gonzalez et al 1993;Kato et al 1993;Sachs et al 1995) (involving a lithium-sensitive coil). In vivo 1 H MRS is a non-invasive technique for measuring metabolite concentrations in living tissue .…”

mentioning

confidence: 99%

Decreased Anterior Cingulate Myo-inositol/Creatine Spectroscopy Resonance with Lithium Treatment in Children with Bipolar Disorder

Davanzo

2001

Neuropsychopharmacology

227

130

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This project was designed to compare differences in brain proton spectra between children and adolescents with bipolar disorder (BPD) and gender and age-matched normal controls, and to measure changes in myo-inositol levels following lithium therapy, utilizing in vivo proton magnetic resonance spectroscopy ( 1 H MRS). A single voxel (2x2x2 cm3) was placed in brain anterior (Tondo et al. 1998). Epidemiological data (Lewinsohn et al. 1995), suggest that the prevalence of juvenile-onset BPD may be as common as rates reported in adult populations, although estimates vary widely (Costello et al. 1996). Given the increased frequency of lithium use among children and adolescents (Ryan et al. 1999) there is a clear need to assess the effects of lithium in pediatric populations. Children may have greater lithium resistance than adults (Himmelhoch and Garfinkel 1986;Hsu 1986), and it may take up to six weeks to determine, based on clinical signs and symptoms, whether a child is responding to treatment. Biological markers of treatment response would be extremely useful, particularly in these times of limited inpatient resources. The present study measured the magnetic resonance of myo-inositol and other metabolites with 1 H MRS in pediatric subjects diagnosed with BPD, before and during lithium therapy, with baseline comparison to normal controls individually matched for age and gender. We hypothesized that lithium would have an effect on the :310-825-0469, Fax: 310-206-4446, E-mail: pdavanzo@mednet.ucla.edu Received April 13, 2000; revised August 25, 2000; accepted September 14, 2000. 360 P. Davanzo et al. N EUROPSYCHOPHARMACOLOGY 2001 -VOL . 24 , NO . 4 magnetic resonance of myo-inositol in the anterior cingulate cortex in children with BPD, as measured by in vivo proton magnetic resonance spectroscopy ( 1 H MRS). Secondarily, we postulated that a decrease in myo-inositol signal in response to lithium might be a predictor of treatment efficacy.Lithium has traditionally been the preferred treatment of the manic phase of bipolar illness in adults, children (Geller and Luby 1997), and adolescents (Strober et al. 1995) with BPD. Open-label (Hsu 1986;Carlson et al. 1992;Strober et al. 1995), and one doubleblind placebo-controlled study of adolescents with substance abuse and mania (Geller et al. 1998) suggest that juveniles with BPD may have somewhat reduced benefit from acute lithium therapy compared with adults. Nevertheless, lithium continues to be widely prescribed among children and adolescents with BPD (Geller and Luby 1997) as well as for young patients presenting with excessive irritability (Fava 1997) and extreme affective dysregulation (Vitiello and Stoff 1997).The precise neurobiological mechanisms whereby lithium reduces acute manic excitement and protects against recurrence of illness remain uncertain. It is apparent that lithium exerts an effect on intracellular second-messenger systems in which activated receptorligand complexes stimulate the turnover of inositolcontaining phospholipids (del Rio et ...

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Lateralized abnormality of high energy phosphate metabolism in the frontal lobes of patients with bipolar disorder detected by phase-encoded³¹P-MRS

Cited by 115 publications

References 34 publications

Selective maximization of ³¹P MR spectroscopic signals of in vivo human brain metabolites at 3T

Selective maximization of ³¹P MR spectroscopic signals of in vivo human brain metabolites at 3T

Neuroplasticity and cellular resilience in mood disorders

Decreased Anterior Cingulate Myo-inositol/Creatine Spectroscopy Resonance with Lithium Treatment in Children with Bipolar Disorder

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Lateralized abnormality of high energy phosphate metabolism in the frontal lobes of patients with bipolar disorder detected by phase-encoded31P-MRS

Cited by 115 publications

References 34 publications

Selective maximization of 31P MR spectroscopic signals of in vivo human brain metabolites at 3T

Selective maximization of 31P MR spectroscopic signals of in vivo human brain metabolites at 3T

Neuroplasticity and cellular resilience in mood disorders

Decreased Anterior Cingulate Myo-inositol/Creatine Spectroscopy Resonance with Lithium Treatment in Children with Bipolar Disorder

Contact Info

Product

Resources

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Lateralized abnormality of high energy phosphate metabolism in the frontal lobes of patients with bipolar disorder detected by phase-encoded³¹P-MRS

Selective maximization of ³¹P MR spectroscopic signals of in vivo human brain metabolites at 3T

Selective maximization of ³¹P MR spectroscopic signals of in vivo human brain metabolites at 3T