MR spectroscopy: potential uses beyond the brain - University of ...

Potential Uses Beyond the Brainin Veterinary MedicineChristopher Warrington, DVMResident, Medical ImagingUniversity of MinnesotaVeterinary Medical Center

In vivo MR Spectroscopy• First reported in the brain in animal models in late1970so Phosphorus-31 ( 31 P)o Measured metabolism• Adenosine triphosphate (ATP)• Phosphocreatine (PCr)• Inorganic Phosphate (Pi)• First in vivo 31 P MRS in humans reported in 1981o Primary focus for MRS during the 1980s was on 31 Po Clinical applications limited• Low spatial resolution and SNR• Requires large voxel volume (>30 cm 3 )Barker PB, et al., 2010.

1H-MR SpectroscopyBarker PB, et al., 2010.• 1983 – first 1 H-MRS in rat brain (8.5T)• 1985 – first 1 H-MRS in human brain (1.5T)• Advantages over 31 Po High natural abundanceo Higher SNR and spatial resolutiono Uses same hardware as conventional MRIo Smaller voxel volumes (1-8 cm 3 at 1.5T)• Primary MRS technique for human brain metabolismsince mid-1980s

Spectrum Acquisition• Define voxel in tissue of interesto Single voxelo Multi-voxel• Proton signal of metabolites withinvoxel used to produce the image• Chemical shift (resonancefrequency) plotted on x-axis (ppm)• Relative metabolite concentrationswithin voxel plotted on y-axis

Normal Brain SpectrumImage from Soares DP and Law M, 2009.

Prostate Spectroscopy• Relatively low sensitivity and specificity of prostate cancer diagnosiswith conventional imaging (US, MRI) in human medicineo Various prostate pathologies can mimic cancer• Chronic prostatitis• Scar tissue• Hemorrhage• Studies report increased sensitivity and specificity with addition of MRSto US, MRI, biopsy, and/or protein-specific antigen (PSA) test• Coil optionso Endorectal coilo External phased-array coilBarker 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 peakso Creatine (Cr) at 3.0 ppmo Choline (Cho) at 3.2 ppmo Myo-Inositol (Ino) at 3.6 ppm• Marker for altered membrane metabolismo +/- Polyamine (spermine) at 3.1 ppm• Metabolite ratioo Based on peak areao Cho + Cr / Cit (CC/C) or Cho/Cito Normal CC/C = 0.22 +/- 0.013 (Jung JA, et al., 2004)Image from Kurhanewicz J, et al., 2000.Barker PB, et al., 2010.

Abnormal Prostate Spectroscopy• Benign Prostatic Hyperplasia (BPH) 1o Increased citrate production by secretory epithelial cellso ↑ Cit peak, therefore ↓ CC/C ratioo Spectrum can look very similar to normal prostate• Prostatitiso Disagreement between studies• ↑ Cit, which decreases to normal following treatment 2Image from Garcia-Segura JM, et al., 1999.Image from Van DorstenFA, et al., 2001.1Garcia-Segura JM, et al., 1999.2Van Dorsten FA, et al., 2001.Pre-therapyPost-therapy

Abnormal Prostate Spectroscopy• Benign Prostatic Hyperplasia (BPH) 1o Increased citrate production by secretory epithelial cellso ↑ Cit peak, therefore ↓ CC/C ratioo Spectrum can look very similar to normal prostate• Prostatitiso Disagreement between studies• ↑ Cit, which decreases to normalfollowing treatment 2• ↓ Cit, to the point of mimickingprostate cancer 3Image from Garcia-Segura JM, et al., 1999.1Garcia-Segura JM, et al., 1999.2Image from Shukla-Van Dorsten FA, et al., 2001.3Dave A, et al., 2004.Shukla-Dave A, et al., 2004.Chronic Prostatitis Normal

Abnormal Prostate Spectroscopy• Prostatic adenocarcinoma 1o Normal glandular epithelial cells replaced by cancer = ↓ Cito Increased cell membrane turnover = ↑ Choo ↑ CC/C ratio, corresponding to degree of malignancyo May also see ↑ Ino• Should be < Cr peak in normal and BPHImage from Garcia-Segura JM, et al., 1999.• Cr/Ino ratio < 1.0 reported as secondary indicatorto discriminate between BPH and carcinoma 2Image from Casciani E, et al., 2006.1Barker PB, et al., 2010.2Garcia-Segura JM, et al., 1999.

Grading Scale for Malignancy 1Normal1Malignant51Jung JA, et al., 2004

Potential Use in Veterinary Medicine?• Possibleo Prostate size – age and breed variation• Volume averaging with surrounding fato Castrated vs. intacto Lower citrate concentrations vs. humans 1o Cost• MRI not routine to evaluate prostateo Accessibility of prostate for imaging and FNA/biopsy• More difficult in humans (intrapelvic)o Questionable differentiation between prostatitis and cancero Needs further investigation1Mobasheri A, et al., 2003.

Breast Spectroscopy• Third-most common clinical use of MRS in human medicine• Characterize breast lesions and determine malignancyo Added specificity to conventional MRI in defining malignant lesions• Hallmark peak is Cho at 3.2 ppmo Increasing Cho peak height correlates with increased malignancyo Elevated Cho more frequently seen in malignant than benign lesionsNormalWeinstein 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 malignancyo Added specificity to conventional MRI in defining malignant lesions• Hallmark peak is Cho at 3.2 ppmo Increasing Cho peak height correlates with increased malignancyo Elevated Cho more frequently seen in malignant than benign lesionsBenign fibrosis andductal hyperplasiaWeinstein 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 malignancyo Added specificity to conventional MRI in defining malignant lesions• Hallmark peak is Cho at 3.2 ppmo Increasing Cho peak height correlates with increased malignancyo Elevated Cho more frequently seen in malignant than benign lesionsDuctalcarcinomaWeinstein S, et al., 2010.Image from Bartella L, et al., 2007.

Potential Use in Veterinary Medicine?• DoubtfulooooSize and periphery of mammary glands• Volume averaging with surrounding fatPeriphery of palpable masses/nodules conducive toFNA or biopsy without imaging guidanceCostPotential for identification of metastasis?• ↑ Cho peak not specific for mammary carcinoma• No metabolite peak specific to mammary-origin cells

Musculoskeletal Spectroscopy• Relatively new procedure in human medicineo Limited reports in the literatureo 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 tumorso Malignant >>> Benigno Active benign lesions – neurofibroma and stress fractures – can show Cho peako Can see discrete Cho peak and increased Cr peak post-operatively• Multi-voxel can be used to assess margins for extent/infiltration of massFayad LM, et al., 2007.

Musculoskeletal SpectroscopyImage from Fayad LM, et al., 2007.“Normal” muscle spectrummyocutaneousflap post- tumor resection

Musculoskeletal SpectroscopyImage from Fayad LM, et al., 2007.Low-grade sarcoma

Musculoskeletal SpectroscopyImage from Fayad LM, et al., 2007.Lipoma

Potential Use in Veterinary Medicine?• Possibleo Size• Larger muscles – accommodate voxel• Smaller muscles – volume averagingo Determine malignancy of musculoskeletal masses (↑ Cho)o Differentiate recurrence of tumor vs. treatment effectso 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 limitationso Motion (primarily respiratory)o Low SNRo Volume averagingNormaladult liverQayyum A, 2009.

• Diffuse liver diseaseoooQuality may not be as affectedSpecific voxel location not as importantAvoid large vessels and edges of liver lobes• Focal liver diseaseooLarge masses – majority of sampling may be representativeSmall masses/nodules – volume averaging• Motion correctionMotion Artifactso Manual/automatic post-processing• Cannot correct for inclusion of different tissueso Respiratory gating• ↓ SNR due to shorter sequence• Slightly different sample volume with each breathQayyum A, 2009.

Diffuse Liver Disease• Hepatic Steatosis (Fatty Liver)o Multiple lipid peaks in liver• Methyl (-CH 3 ) at 0.9-1.1 ppm• Methylene (-CH 2 ) at 1.3-1.6 ppmo Total lipid/water ratio increases with steatosis grade (0 to 3)• Metabolite changes indicative of inflammation orfibrosis have not been clearly establishedQayyum A, 2009.

Hepatic Steatosis (Fatty Liver)NormalFatty liverdiseaseQayyum A, 2009.

Focal Liver Disease• Hepatocellular Carcinomao ↑ Cho relative to lipids• Ability to distinguish benign and malignant tumors fromnormal liver parenchyma has not been established• Relatively large amounts of choline-containingcompounds may occur in normal liver• More susceptible to motion artifactQayyum A, 2009.

Potential Use in Veterinary Medicine?• Possibleo Hepatic lipidosis• Different fat content in animal liver vs. human liver?• Varying “baseline” fat content- lean vs. obese? dog vs. cat? breeddifferences?o Diffuse liver diseaseso Regenerative nodules vs. malignant tumorso Costo Anesthetic drug effects on liver MRS?o Liver sizeo Motion artifacts

Summary• Human medicineo MRS routinely used as a diagnostic tool with conventional MRIo Decades of research and experienceo Higher strength MRI units allow ↑ SNR and resolution• Veterinary Medicineo Virtually no MRS data to this pointo Technically challenging due to small patient sizeo Costo Potential areas of benefito Improving technology and availability of higher strength MRI

References1. Barker PB, Bizzi A, De Stefano N, et al. Clinical MR Spectroscopy: Techniques andApplications. New York: Cambridge University Press, 2010.2. Soares DP, Law M. Magnetic resonance spectroscopy of the brain: review ofmetabolites and clinical applications. Clinical Radiology 2009; 64(1): 12-21.3. Teresi LM. A Practicing Radiologist Guide to MR Spectroscopy of the Brain. XlibrisCorp., 2007; 14-20.4. Kurhanewicz J, Vigneron DB, Males RG, et al. The prostate: MR imaging andspectroscopy. Present and future. Radiol Clin North Am 2000; 38: 115-38.5. Garcia-Segura JM, Sanchez-Chapado M, Ibarburen C, et al. In vivo protonmagnetic resonance spectroscopy of diseased prostate: spectroscopic features ofmalignant versus benign pathology. Mag Reson Imag 1999; 17(5): 755-765.6. Van Dorsten FA, Engelbrecht M, Van der Graaf M, et al. Differentiation ofProstatitis from Prostate Carcinoma Using 1 H MR Spectroscopic Imaging andDynamic 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 Imagingand 1 H MR Spectroscopic Imaging Findings–Initial Observations. Radiology 2004;231: 717-724.

References8. Casciani E, Gualdi GF. Prostate cancer: value of magnetic resonancespectroscopy 3D chemical shift imaging. Abdom Imaging 2006; 31: 490-499.9. Jung JA, Coakley FV, Vigneron DB, et al. Prostate depiction at endorectal MRspectroscopic 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 downregulatedin canine prostate cancer; a possible consequence of metabolictransformation in the process of prostate malignancy. Cancer Cell International2003; 3(8).11. Weinstein S, Rosen M. Breast MR Imaging: Current Indications and AdvancedImaging Techniques. Radiol Clin N Am 2010; 48: 1013-1042.12. Bartella L, Huang W. Proton ( 1 H) MR Spectroscopy of the Breast. Radiographics2007; 27: S241-S252.13. Fayad LM, Barker PB, Jacobs MA, et al. Characterization of MusculoskeletalLesions on 3-T Proton MR Spectroscopy. American Journal of Roentgenology2007; 188(6): 1513-1520.14. Qayyum A. MR Spectroscopy of the Liver: Principles and Clinical Applications.Radiographics 2009; 29: 1653-1664.

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