MR spectroscopy: potential uses beyond the brain - University of ...
MR spectroscopy: potential uses beyond the brain - University of ...
MR spectroscopy: potential uses beyond the brain - University of ...
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Potential Uses Beyond <strong>the</strong> Brainin Veterinary MedicineChristopher Warrington, DV<strong>MR</strong>esident, Medical Imaging<strong>University</strong> <strong>of</strong> MinnesotaVeterinary Medical Center
In vivo <strong>MR</strong> Spectroscopy• First reported in <strong>the</strong> <strong>brain</strong> 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 <strong>MR</strong>S in humans reported in 1981o Primary focus for <strong>MR</strong>S during <strong>the</strong> 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-<strong>MR</strong> SpectroscopyBarker PB, et al., 2010.• 1983 – first 1 H-<strong>MR</strong>S in rat <strong>brain</strong> (8.5T)• 1985 – first 1 H-<strong>MR</strong>S in human <strong>brain</strong> (1.5T)• Advantages over 31 Po High natural abundanceo Higher SNR and spatial resolutiono Uses same hardware as conventional <strong>MR</strong>Io Smaller voxel volumes (1-8 cm 3 at 1.5T)• Primary <strong>MR</strong>S technique for human <strong>brain</strong> metabolismsince mid-1980s
Spectrum Acquisition• Define voxel in tissue <strong>of</strong> interesto Single voxelo Multi-voxel• Proton signal <strong>of</strong> metabolites withinvoxel used to produce <strong>the</strong> 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 <strong>of</strong> prostate cancer diagnosiswith conventional imaging (US, <strong>MR</strong>I) in human medicineo Various prostate pathologies can mimic cancer• Chronic prostatitis• Scar tissue• Hemorrhage• Studies report increased sensitivity and specificity with addition <strong>of</strong> <strong>MR</strong>Sto US, <strong>MR</strong>I, 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 <strong>of</strong> citrate (Cit)o Strong peak at 2.6 ppm (usually coupled)• O<strong>the</strong>r 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 epi<strong>the</strong>lial cellso ↑ Cit peak, <strong>the</strong>refore ↓ 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-<strong>the</strong>rapyPost-<strong>the</strong>rapy
Abnormal Prostate Spectroscopy• Benign Prostatic Hyperplasia (BPH) 1o Increased citrate production by secretory epi<strong>the</strong>lial cellso ↑ Cit peak, <strong>the</strong>refore ↓ CC/C ratioo Spectrum can look very similar to normal prostate• Prostatitiso Disagreement between studies• ↑ Cit, which decreases to normalfollowing treatment 2• ↓ Cit, to <strong>the</strong> point <strong>of</strong> 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 epi<strong>the</strong>lial cells replaced by cancer = ↓ Cito Increased cell membrane turnover = ↑ Choo ↑ CC/C ratio, corresponding to degree <strong>of</strong> 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• <strong>MR</strong>I not routine to evaluate prostateo Accessibility <strong>of</strong> prostate for imaging and FNA/biopsy• More difficult in humans (intrapelvic)o Questionable differentiation between prostatitis and cancero Needs fur<strong>the</strong>r investigation1Mobasheri A, et al., 2003.
Breast Spectroscopy• Third-most common clinical use <strong>of</strong> <strong>MR</strong>S in human medicine• Characterize breast lesions and determine malignancyo Added specificity to conventional <strong>MR</strong>I 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 <strong>of</strong> <strong>MR</strong>S in human medicine• Characterize breast lesions and determine malignancyo Added specificity to conventional <strong>MR</strong>I 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 <strong>of</strong> <strong>MR</strong>S in human medicine• Characterize breast lesions and determine malignancyo Added specificity to conventional <strong>MR</strong>I 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 <strong>of</strong> mammary glands• Volume averaging with surrounding fatPeriphery <strong>of</strong> palpable masses/nodules conducive toFNA or biopsy without imaging guidanceCostPotential for identification <strong>of</strong> 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 <strong>the</strong> 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 – neur<strong>of</strong>ibroma 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 <strong>of</strong> 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 <strong>of</strong> musculoskeletal masses (↑ Cho)o Differentiate recurrence <strong>of</strong> tumor vs. treatment effectso Needs fur<strong>the</strong>r investigation
Liver Spectroscopy• Relatively new <strong>MR</strong>S technique in human medicine• Characterize diffuse liver disease• Quantify lipid content in <strong>the</strong> 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 <strong>of</strong> liver lobes• Focal liver diseaseooLarge masses – majority <strong>of</strong> sampling may be representativeSmall masses/nodules – volume averaging• Motion correctionMotion Artifactso Manual/automatic post-processing• Cannot correct for inclusion <strong>of</strong> 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 <strong>of</strong> 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 <strong>of</strong> 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 Anes<strong>the</strong>tic drug effects on liver <strong>MR</strong>S?o Liver sizeo Motion artifacts
Summary• Human medicineo <strong>MR</strong>S routinely used as a diagnostic tool with conventional <strong>MR</strong>Io Decades <strong>of</strong> research and experienceo Higher strength <strong>MR</strong>I units allow ↑ SNR and resolution• Veterinary Medicineo Virtually no <strong>MR</strong>S data to this pointo Technically challenging due to small patient sizeo Costo Potential areas <strong>of</strong> benefito Improving technology and availability <strong>of</strong> higher strength <strong>MR</strong>I
References1. Barker PB, Bizzi A, De Stefano N, et al. Clinical <strong>MR</strong> Spectroscopy: Techniques andApplications. New York: Cambridge <strong>University</strong> Press, 2010.2. Soares DP, Law M. Magnetic resonance <strong>spectroscopy</strong> <strong>of</strong> <strong>the</strong> <strong>brain</strong>: review <strong>of</strong>metabolites and clinical applications. Clinical Radiology 2009; 64(1): 12-21.3. Teresi LM. A Practicing Radiologist Guide to <strong>MR</strong> Spectroscopy <strong>of</strong> <strong>the</strong> Brain. XlibrisCorp., 2007; 14-20.4. Kurhanewicz J, Vigneron DB, Males RG, et al. The prostate: <strong>MR</strong> imaging and<strong>spectroscopy</strong>. 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 <strong>spectroscopy</strong> <strong>of</strong> diseased prostate: spectroscopic features <strong>of</strong>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 <strong>of</strong>Prostatitis from Prostate Carcinoma Using 1 H <strong>MR</strong> Spectroscopic Imaging andDynamic Contrast-Enhanced <strong>MR</strong>I. Proc Intl Soc Mag Reson Med 2001; 9: 632.7. Shukla-Dave A, Hricak H, Eberhardt SC, et al. Chronic Prostatitis: <strong>MR</strong> Imagingand 1 H <strong>MR</strong> Spectroscopic Imaging Findings–Initial Observations. Radiology 2004;231: 717-724.
References8. Casciani E, Gualdi GF. Prostate cancer: value <strong>of</strong> magnetic resonance<strong>spectroscopy</strong> 3D chemical shift imaging. Abdom Imaging 2006; 31: 490-499.9. Jung JA, Coakley FV, Vigneron DB, et al. Prostate depiction at endorectal <strong>MR</strong>spectroscopic imaging: Investigation <strong>of</strong> a standardized evaluation system.Radiology 2004; 233: 701-08.10. Mobasheri A, Fox R, Evans I, et al. Epi<strong>the</strong>lial Na, K-ATPase expression is downregulatedin canine prostate cancer; a possible consequence <strong>of</strong> metabolictransformation in <strong>the</strong> process <strong>of</strong> prostate malignancy. Cancer Cell International2003; 3(8).11. Weinstein S, Rosen M. Breast <strong>MR</strong> Imaging: Current Indications and AdvancedImaging Techniques. Radiol Clin N Am 2010; 48: 1013-1042.12. Bartella L, Huang W. Proton ( 1 H) <strong>MR</strong> Spectroscopy <strong>of</strong> <strong>the</strong> Breast. Radiographics2007; 27: S241-S252.13. Fayad LM, Barker PB, Jacobs MA, et al. Characterization <strong>of</strong> MusculoskeletalLesions on 3-T Proton <strong>MR</strong> Spectroscopy. American Journal <strong>of</strong> Roentgenology2007; 188(6): 1513-1520.14. Qayyum A. <strong>MR</strong> Spectroscopy <strong>of</strong> <strong>the</strong> Liver: Principles and Clinical Applications.Radiographics 2009; 29: 1653-1664.
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