1. No category

Potential Uses Beyond the Brain
in Veterinary Medicine
Christopher Warrington, DVM
Resident, Medical Imaging
University of Minnesota
Veterinary Medical Center
In vivo MR Spectroscopy
• First reported in the brain in animal models in late
1970s
o Phosphorus-31 (31P)
o Measured metabolism
 Adenosine triphosphate (ATP)
 Phosphocreatine (PCr)
 Inorganic Phosphate (Pi)
• First in vivo 31P MRS in humans reported in 1981
o Primary focus for MRS during the 1980s was on 31P
o Clinical applications limited
 Low spatial resolution and SNR
 Requires large voxel volume (>30 cm3)
Barker PB, et al., 2010.
1H-MR Spectroscopy
• 1983 – first 1H-MRS in rat brain (8.5T)
• 1985 – first 1H-MRS in human brain (1.5T)
• Advantages over 31P
o
o
o
o
High natural abundance
Higher SNR and spatial resolution
Uses same hardware as conventional MRI
Smaller voxel volumes (1-8 cm3 at 1.5T)
• Primary MRS technique for human brain metabolism
since mid-1980s
Barker PB, et al., 2010.
Spectrum Acquisition
• Define voxel in tissue of interest
o Single voxel
o Multi-voxel
• Proton signal of metabolites within
voxel used to produce the image
• Chemical shift (resonance
frequency) plotted on x-axis (ppm)
• Relative metabolite concentrations
within voxel plotted on y-axis
Normal Brain Spectrum
Image from Soares DP and Law M, 2009.
Prostate Spectroscopy
• Relatively low sensitivity and specificity of prostate cancer diagnosis
with conventional imaging (US, MRI) in human medicine
o Various prostate pathologies can mimic cancer
 Chronic prostatitis
 Scar tissue
 Hemorrhage
• Studies report increased sensitivity and specificity with addition of MRS
to US, MRI, biopsy, and/or protein-specific antigen (PSA) test
• Coil options
o Endorectal coil
o External phased-array coil
Barker PB, et al., 2010.
Normal Prostate Spectrum
• Normal prostate contains high levels of citrate (Cit)
o Strong peak at 2.6 ppm (usually coupled)
• Other prominent peaks
o Creatine (Cr) at 3.0 ppm
o Choline (Cho) at 3.2 ppm
o Myo-Inositol (Ino) at 3.6 ppm

Marker for altered membrane metabolism
o +/- Polyamine (spermine) at 3.1 ppm
• Metabolite ratio
o Based on peak area
Image from Kurhanewicz J, et al., 2000.
o Cho + Cr / Cit (CC/C) or Cho/Cit
o Normal CC/C = 0.22 +/- 0.013 (Jung JA, et al., 2004)
Barker PB, et al., 2010.
Abnormal Prostate Spectroscopy
• Benign Prostatic Hyperplasia (BPH) 1
o Increased citrate production by secretory epithelial cells
o ↑ Cit peak, therefore ↓ CC/C ratio
o Spectrum can look very similar to normal prostate
• Prostatitis
Image from Garcia-Segura JM, et al., 1999.
o Disagreement between studies
•
↑ Cit, which decreases to normal following treatment2
Image from Van Dorsten
FA, et al., 2001.
1Garcia-Segura
JM, et al., 1999.
2Van Dorsten FA, et al., 2001.
Pre-therapy
Post-therapy
Abnormal Prostate Spectroscopy
• Benign Prostatic Hyperplasia (BPH) 1
o Increased citrate production by secretory epithelial cells
o ↑ Cit peak, therefore ↓ CC/C ratio
o Spectrum can look very similar to normal prostate
• Prostatitis
o Disagreement between studies
•
Image from Garcia-Segura JM, et al., 1999.
↑ Cit, which decreases to normal
following treatment2
•
↓ Cit, to the point of mimicking
prostate cancer3
1Garcia-Segura
JM, et al., 1999.
Dorsten FA, et al., 2001.
3Shukla-Dave A, et al., 2004.
2Van
Image from ShuklaDave A, et al., 2004.
Chronic Prostatitis
Normal
Abnormal Prostate Spectroscopy
• Prostatic adenocarcinoma 1
o Normal glandular epithelial cells replaced by cancer = ↓ Cit
o Increased cell membrane turnover = ↑ Cho
o ↑ CC/C ratio, corresponding to degree of malignancy
o May also see ↑ Ino


Should be < Cr peak in normal and BPH
Cr/Ino ratio < 1.0 reported as secondary indicator
to discriminate between BPH and carcinoma2
1Barker
PB, et al., 2010.
2Garcia-Segura JM, et al., 1999.
Image from Garcia-Segura JM, et al., 1999.
Image from Casciani E, et al., 2006.
Grading Scale for Malignancy1
Normal
1
1Jung JA,
et al., 2004
Malignant
5
Potential Use in Veterinary Medicine?
• Possible
o Prostate size – age and breed variation
 Volume averaging with surrounding fat
o Castrated vs. intact
o Lower citrate concentrations vs. humans1
o Cost
 MRI not routine to evaluate prostate
o Accessibility of prostate for imaging and FNA/biopsy
 More difficult in humans (intrapelvic)
o Questionable differentiation between prostatitis and cancer
o Needs further investigation
1Mobasheri A,
et al., 2003.
Breast Spectroscopy
• Third-most common clinical use of MRS in human medicine
• Characterize breast lesions and determine malignancy
o Added specificity to conventional MRI in defining malignant lesions
• Hallmark peak is Cho at 3.2 ppm
o Increasing Cho peak height correlates with increased malignancy
o Elevated Cho more frequently seen in malignant than benign lesions
Normal
Weinstein S, et al., 2010.
Image from Bartella L, et al., 2007.
Breast Spectroscopy
• Third-most common clinical use of MRS in human medicine
• Characterize breast lesions and determine malignancy
o Added specificity to conventional MRI in defining malignant lesions
• Hallmark peak is Cho at 3.2 ppm
o Increasing Cho peak height correlates with increased malignancy
o Elevated Cho more frequently seen in malignant than benign lesions
Benign fibrosis and
ductal hyperplasia
Weinstein S, et al., 2010.
Image from Bartella L, et al., 2007.
Breast Spectroscopy
• Third-most common clinical use of MRS in human medicine
• Characterize breast lesions and determine malignancy
o Added specificity to conventional MRI in defining malignant lesions
• Hallmark peak is Cho at 3.2 ppm
o Increasing Cho peak height correlates with increased malignancy
o Elevated Cho more frequently seen in malignant than benign lesions
Ductal
carcinoma
Weinstein S, et al., 2010.
Image from Bartella L, et al., 2007.
Potential Use in Veterinary Medicine?
• Doubtful
o Size and periphery of mammary glands
 Volume averaging with surrounding fat
o Periphery of palpable masses/nodules conducive to
FNA or biopsy without imaging guidance
o Cost
o Potential for identification of metastasis?


↑ Cho peak not specific for mammary carcinoma
No metabolite peak specific to mammaryorigin cells
Musculoskeletal Spectroscopy
• Relatively new procedure in human medicine
o Limited reports in the literature
o First report ~ 2000
• Mainly utilized in research at this time
• Choline and creatine peaks are present in metabolically active muscle
• High lipid and water peaks, which may obscure smaller adjacent peaks
• ↑ Cho peak with active tumors
o Malignant >>> Benign
o Active benign lesions – neurofibroma and stress fractures – can show Cho peak
o Can see discrete Cho peak and increased Cr peak post-operatively
•
Multi-voxel can be used to assess margins for extent/infiltration of mass
Fayad LM, et al., 2007.
Musculoskeletal Spectroscopy
Image from Fayad LM, et al., 2007.
“Normal” muscle spectrummyocutaneous flap post- tumor resection
Musculoskeletal Spectroscopy
Image from Fayad LM, et al., 2007.
Low-grade sarcoma
Musculoskeletal Spectroscopy
Image from Fayad LM, et al., 2007.
Lipoma
Potential Use in Veterinary Medicine?
• Possible
o Size
 Larger muscles – accommodate voxel
 Smaller muscles – volume averaging
o Determine malignancy of musculoskeletal masses (↑ Cho)
o Differentiate recurrence of tumor vs. treatment effects
o Needs further investigation
Liver Spectroscopy
• Relatively new MRS technique in human medicine
• Characterize diffuse liver disease
• Quantify lipid content in the liver
• Diagnose malignancy (↑ Cho)
• High water and lipid peaks may obscure smaller peaks
• Technical limitations
o Motion (primarily respiratory)
o Low SNR
o Volume averaging
Qayyum A, 2009.
Normal
adult liver
Motion Artifacts
• Diffuse liver disease
o Quality may not be as affected
o Specific voxel location not as important
o Avoid large vessels and edges of liver lobes
• Focal liver disease
o Large masses – majority of sampling may be representative
o Small masses/nodules – volume averaging
• Motion correction
o Manual/automatic post-processing

Cannot correct for inclusion of different tissues
o Respiratory gating


↓ SNR due to shorter sequence
Slightly different sample volume with each breath
Qayyum A, 2009.
Diffuse Liver Disease
• Hepatic Steatosis (Fatty Liver)
o Multiple lipid peaks in liver
 Methyl (-CH3) at 0.9-1.1 ppm
 Methylene (-CH2) at 1.3-1.6 ppm
o Total lipid/water ratio increases with steatosis grade (0 to 3)
• Metabolite changes indicative of inflammation or
fibrosis have not been clearly established
Qayyum A, 2009.
Hepatic Steatosis (Fatty Liver)
Normal
Fatty liver
disease
Qayyum A, 2009.
Focal Liver Disease
• Hepatocellular Carcinoma
o ↑ Cho relative to lipids
• Ability to distinguish benign and malignant tumors from
normal liver parenchyma has not been established
• Relatively large amounts of choline-containing
compounds may occur in normal liver
• More susceptible to motion artifact
Qayyum A, 2009.
Potential Use in Veterinary Medicine?
• Possible
o Hepatic lipidosis


o
o
o
o
o
o
Different fat content in animal liver vs. human liver?
Varying “baseline” fat content- lean vs. obese? dog vs. cat? breed
differences?
Diffuse liver diseases
Regenerative nodules vs. malignant tumors
Cost
Anesthetic drug effects on liver MRS?
Liver size
Motion artifacts
Summary
• Human medicine
o MRS routinely used as a diagnostic tool with conventional MRI
o Decades of research and experience
o Higher strength MRI units allow ↑ SNR and resolution
• Veterinary Medicine
o Virtually no MRS data to this point
o Technically challenging due to small patient size
o Cost
o Potential areas of benefit
o Improving technology and availability of higher strength MRI
References
1. Barker PB, Bizzi A, De Stefano N, et al. Clinical MR Spectroscopy: Techniques and
Applications. New York: Cambridge University Press, 2010.
2. Soares DP, Law M. Magnetic resonance spectroscopy of the brain: review of
metabolites and clinical applications. Clinical Radiology 2009; 64(1): 12-21.
3. Teresi LM. A Practicing Radiologist Guide to MR Spectroscopy of the Brain. Xlibris
Corp., 2007; 14-20.
4. Kurhanewicz J, Vigneron DB, Males RG, et al. The prostate: MR imaging and
spectroscopy. Present and future. Radiol Clin North Am 2000; 38: 115-38.
5. Garcia-Segura JM, Sanchez-Chapado M, Ibarburen C, et al. In vivo proton
magnetic resonance spectroscopy of diseased prostate: spectroscopic features of
malignant versus benign pathology. Mag Reson Imag 1999; 17(5): 755-765.
6. Van Dorsten FA, Engelbrecht M, Van der Graaf M, et al. Differentiation of
Prostatitis from Prostate Carcinoma Using 1H MR Spectroscopic Imaging and
Dynamic Contrast-Enhanced MRI. Proc Intl Soc Mag Reson Med 2001; 9: 632.
7. Shukla-Dave A, Hricak H, Eberhardt SC, et al. Chronic Prostatitis: MR Imaging
and 1H MR Spectroscopic Imaging Findings–Initial Observations. Radiology 2004;
231: 717-724.
References
8. Casciani E, Gualdi GF. Prostate cancer: value of magnetic resonance
spectroscopy 3D chemical shift imaging. Abdom Imaging 2006; 31: 490-499.
9. Jung JA, Coakley FV, Vigneron DB, et al. Prostate depiction at endorectal MR
spectroscopic imaging: Investigation of a standardized evaluation system.
Radiology 2004; 233: 701-08.
10. Mobasheri A, Fox R, Evans I, et al. Epithelial Na, K-ATPase expression is downregulated in canine prostate cancer; a possible consequence of metabolic
transformation in the process of prostate malignancy. Cancer Cell International
2003; 3(8).
11. Weinstein S, Rosen M. Breast MR Imaging: Current Indications and Advanced
Imaging Techniques. Radiol Clin N Am 2010; 48: 1013-1042.
12. Bartella L, Huang W. Proton (1H) MR Spectroscopy of the Breast. Radiographics
2007; 27: S241-S252.
13. Fayad LM, Barker PB, Jacobs MA, et al. Characterization of Musculoskeletal
Lesions on 3-T Proton MR Spectroscopy. American Journal of Roentgenology
2007; 188(6): 1513-1520.
14. Qayyum A. MR Spectroscopy of the Liver: Principles and Clinical Applications.
Radiographics 2009; 29: 1653-1664.
Questions?