Analysis of Brain T1/T2 Ratio Histogram in the Patients with Sickle Cell Disease

Comparing with the Normal Controls

Memi Watanabe1, Karen Buch1, Hernan Jara1,Kotaro Sekiya1, and Osamu Sakai1,2,3

Departments of 1Radiology, 2Otolaryngology–Head and Neck Surgery, and 3Radiation Oncology Boston Medical Center, Boston University School of Medicine, Boston, MA

Presentation Number: EP-59

Disclosures

HJ: Activities related to the present work: disclosed no relevant relationships. Activities not related to the present work: institution received a grant from GE Healthcare.

Introduction (I)

• Cerebral complications associated with sickle cell disease (SCD) include cerebral infarction, intracranial hemorrhage, and neurocognitive impairment.• Those complications can lead to life-long disabilities and even death.• Conventional imaging techniques have limited sensitivity and specificity to identify patients at risk.

Introduction (II)

• T1 and T2 are temporal measures of equilibration of the longitudinal and transverse magnetizations respectively.• Although T1 and T2 contain different physical information, some information is common.

Introduction (III)

• Calculating the T1/T2 ratio is step towards “purifying” the physical information content of T1, thus potentially increasing its sensitivity and specificity to disease*.

T1 T2 T1/T2

(*) Farraher SW, Jara H, Chang KJ, Ozonoff A, Soto JA. Differentiation of hepatocellular carcinoma and hepatic metastasis from cysts and hemangiomas with calculated T2 relaxation times and the T1/T2 relaxation times ratio. J Magn Reson Imaging 2006;24(6):1333-1341.

Purpose

The purpose of this study was to investigate the manifestations of brain abnormalities in patients with SCD using quantitative MRI (qMRI) parameters, specifically T1/T2 ratio and T1 and T2 relaxation times.

SubjectsFollowing IRB* approval and HIPAA** compliance, 14 SCD patients and 12 age-matched patient controls without apparent abnormalities on conventional brain MRI.

SCD controlGender 5 males : 9 females 4 males : 8 females

Age 19.8 - 43 years (mean 29.3 years)

17 – 48.6 years (mean 36.6 years)

Materials and Methods

Inclusion criteria for controlsNormal brain parenchyma on MR studies, including nonspecific white matter T2 hyperintensities <5mm, <3 lesions

* IRB: internal review board* * HIPAA: Health Insurance Portability and Accountability Act guidelines of the National Institutes of Health

Image acquisition

Sequence: Institutional clinical protocol (T1WI, fat-suppressed GRASE* T2WI, FLAIR, FFE*, DWI) and mixed turbo spin echo (mixed-TSE) pulse sequence*GRASE: gradient and spin echo , *FFE: fast field echo

Key imaging parameters for mixed-TSE: effective echo time 7.142 and 100 ms, repetition time 14,882 ms, inversion time 700 and 7,441 ms, echo train length 18 (9 per echo: centric, liner)

MRI: 1.5T (Achieva or Intera, Philips Medical Systems, Cleveland, OH)

Image processing

Mixed-TSE dataset

Segmentation of the whole intracranial volume

Histogram generation:T1 and T2 relaxation times, T1/T2 ratio

Gaussian analysis: peak histogram values

Between-group comparison

SCD vs. Controls:• No significant difference in age (p=0.06)

SubjectsResults

MRI findings in SCD patients (n=14):Abnormal MRI (n=7)

Multiple old infarcts, non-specific T2 hyperintense foci, and mild atrophy

Normal MRI (n=7)

T1 histogram• bi-modal (GM and WM)• long T1 for CSF

HistogramsResults

GM

CSFWM

CSF

WM+GM

WMGM

CSF

T2 histogram• mono-modal (GM+WM)• long T2 for CSF

T1/T2 ratio histogram• bi-modal (GM and WM)

T1 (ms)

T2 (ms)

T1/T2 ratio

Pixel frequency

Pixel frequency

Pixel frequency

T1 peak values vs. Age

No significant difference between SCD and controls for T1 histograms

• GM peaks: p=0.83• WM peaks: p=0.47

Age (years)

T2 peak values vs. Age

No significant differences between SCD and controls in T2 histograms

• T2 histogram peaks: p=0.09

Age (years)

T1/T2 ratio peak values vs. Age

Significant differences between SCD and controls for T1/T2 ratio histograms

• GM peaks: p<0.0001• WM peaks: p=0.046

Age (years)

T1/T2 ratio peak values vs. Age

• Lower GM peak values in SCD subjects• Age-associated decreases in GM peak values in SCD • Slight increases in GM peaks in controls

Age (years)

Brain MR relaxometry in SCDBrain T1 measurements in SCD children vs..

controls (Steen et al, 1998 and 1999)• Significantly lower T1 in caudate, thalamus, and

cortex in SCD patients normal by conventional MRI• Significant decline in T1 with increasing disease

seventy in the cortical GM and caudate• Significant increase in WM T1 only in the later

stage of the disease

Discussion

Vulnerability of the gray matter

Diffusion studies in SCD• Decline in fractional anisotropy (FA),

increases in apparent diffusion coefficient (ADC) within brain regions, including corpus callosum, frontal WM, centrum semiovale, periventricular areas, head of the caudate nucleus, thalamus, and brainstem

• Reductions in fiber counts• Correlations of increased ADC with

deficiencies in cognitive function

Disrupted white matter integrityPossible association with cognitive impairment

T1/T2 ratio histogram analysis in SCD

• Significant differences in GM peak- Lower GM peak values- Age-associated decline in GM peak values

• Statistically significant decreases in WM peak values

• While T1 and T2 histograms did not show statistically significant differences

Suggestive of damages within GM and WMLarger differences in GM parameters

Conclusion

• This study shows significant differences between SCD and control group in GM peak values of the T1/T2 ratio histogram.

• T1 and T2 histograms did not show statistically significant differences between SCD patients and controls.

• The T1/T2 ratio of the brain may be more sensitive and useful for the quantitative assessment of the pathological conditions including SCD.

• The assessment of the association with cognitive impairment with a larger number of SDC patients including children is anticipated.

Conclusion

References

Corresponding AuthorMemi Watanabe, MD.

Department of Radiology, Boston Medical Center Boston University School of Medicine

E-mail address: Memi.Watanabe@bmc.org

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