Kidney Stone Diagnosis and Managment

HARVARD MEDICAL SCHOOL Kidney Stone Diagnosis and Managment Dushyant Sahani MD

Disclosures MGH has research agreement GE Health Care Siemens Medical Systems

Clinical Perspective Prevalence of Urolithiasis 3.2% 5.2% Rising Prevalence 1970s 1980s 1990s Urolithiasis has a life time risk of 10-15% It has a high relapse rate (50% in 5-10 yrs and 75% in 20 yrs) Affects Men more than women Common clinical presentation Acute flank pain and hematuria Curhan, G.C., Epidemiology of stone disease. Urol Clin North Am, 2007. 34(3): p. 287-93.

MDCT in Urolithiasis Unenhanced CT - Initial investigation of choice in suspected urolithiasis 22% of all CT performed in the ER for acute abdomen pain Highly accurate test (Sensitivity = 95-98% & Specificity =96-100%) Detects other causes of acute flank pain Identification of ureterolithiasis at imaging altered management in nearly 55% 60% of patients suspected of having acute renal colic. Reveals associated abnormalities like congenital abnormalities, infections and neoplasms Rosen MP et al. Eur Radiol 2003;13(2):418 424. Dalrymple NC et al. J Urol 1998;159(3):735 740. Wrenn K. Ann Emerg Med 1995;26(3):304 307.

Stone Types Radioopacity Composition Occurrence On KUB On CT Calcium oxalate monohydrate (COM) & dehydrate (COD) Hydroxyapatite (Calcium phosphate) 40-60% Radio-opaque Radio-opaque 20-60% Radio-opaque Radio-opaque Brushite 2-4% Radio-opaque Radio-opaque Uric Acid 5-10% Radio- lucent Radio-opaque Struvite 5-15% Radio-opaque Radio-opaque Cystine 1-2.5% Mildly Opaque Radio-opaque

MDCT Technique Scan Coverage - Upper pole of kidneys to the base of the bladder Patient preparation - Bladder distension to visualize stones within the distal ureter Slice thickness 3-5 mm Pitch -1-1.6 Coronal Reformations (2.5-3mm)

Urolithiasis CT Diagnostic Signs Virtually all stones are radio-opaque on CT (>200HU) Primary sign of Ureterolithiasis Stone in the ureter (target sign) with proximal hydroureter Stones radiolucent on CT - Pure matrix stones and stones made of pure Indinavir (Indinavir - Protease inhibitor used in the treatment of HIV)

Value of Coronal Reformations 1 2 Improved detection of stones unrecognized on axial images Improved detection of small ureteral and renal calculi at poles Phleboliths and calcified vascular plaques from urinary stones Enhances radiologist confidence Benefits the urologists in treatment decision Lin WC et al. J Urol 2007.

Factors Influencing Treatment Decision Urologic intervention is influenced by 3 crucial factors Stone size/ location Patient Symptoms Stone Composition Presence of obstruction is not the primary factor considered for urologic intervention Bierkens AF et al. Br J Urol. 1998. Eisner BH et al. Urology 2008. Phipps S et al. Ann R Coll Surg Eng 2010.

Stone Burden Assessment Stone burden (stone size and volume) determines the type of procedure ESWL or Ureteroscopy is performed for stones <1cm PCNL for stones >1.5cm Stone Size Accurate stone size measurement is paramount to plan treatment options The ideal method for accurate measurement on CT is to measure using bone window settings (1250 X 250) and magnification 8mm 6 mm Soft tissue window Bone window with Magnification Eisner BH et al. J Urol 2009

Stone Size & Treatment Decisions Stone < 5mm (98% for stones < or = 4mm pass spontaneously) Stones > 6mm & <15mm Stone >15mm or Staghorn Calculi (6-9 mm uereteral stone 60-25% pass) Stone location predicts outcome Upper=48%, mid=60%, lower 75-79% likely to pass spontaneously Medical Expulsive therapy (Alpha blockers) Intervene for unremitting pain, nausea, fever, failure to passage on medical therapy Extracorporeal Shockwave lithotripsy (ESWL) Ureteroscopic lithotripsy (upper ureter or larger stone) Percutaneous Nephrolithotomy (PCNL) Bierkens AF et al. Br J Urol. 1998. Coll DM et al. AJR 2002. Eisner BH et al. Urology 2008. Phipps S et al. Ann R Coll Surg Eng 2010.

Stone Volumetry 22 cc Threshold based CAD Algorithms or manual semiautomated methods Linear measurement not suitable in irregularly contoured stones like stag horn calculi Measuring the stone volume eliminates this problem Total stone volume is an appropriate measure of stone burden Demehri S et al. AJR 2012. Singh Ak et al. RSNA 2010.

ESWL Failure: Multivariate CT characteristics Independent Variables (Dependent Variable= failure rate) Area-Under Curve (AUC) Cut-off value Sensitivity; Specificity (%) 95% Confidence Interval (CI) P=value Stone Volume CAD 0.895 >712.54 mm 3 80;80 0.745-0.964 P<0.0001 Stone Volume- 0.872 >564.75 mm 3 88;73 0.728-0.956 P<0.0001 Products Maximum Stone 0.839 >8.89mm 96;60 0.688-0.936 P<0.0001 Size Number of Stones 0.755 >2 52;86 0.593-0.877 P=0.0002 Mean Stone Size 0.735 >6.25mm 92;46.7 0.571-0.861 P=0.0002 Age 0.524 <50y 96;33 0.360-0.684 P=8267 Overall model fit (Chi square)=21.818; p=0.0006 Singh Ak et al. RSNA 2010.

Stone Composition & Treatment Decisions <400 HU > 500 HU Uric Acid Stone Medical Management Allopurinol Treatment of Hyperuricemia <1000 HU (Struvite) ESWL >1000HU (Brushite, Cystine, COM) Ureteroscopy PCNL Hamm M et al. J Urol 2002. Parker BD et al. Urology 2004

MDCT and Stone Composition Stone composition can be determined using HU CT Attenuation values 64-77% accuracy in determination of stone composition, is not robust and reliable Stone Composition Uric Acid Struvite Cystine Calcium Phosphate COM and Brushite Attenuation value at 120kVp 200-450 HU 600-900 HU 600-1100 HU 1200-1600 HU 1700-2800 HU Stone composition also effects the efficacy of ESWL (Brushite, cystine and COM stones are hard and resistant, while struvite stones usually fragment easily) Dretler SP. J Endourol 2001 Motley G et al. Urol 2001 Eisner BH et al. J Urol 2009 KulkarniN et al. JCAT (in-press)

DECT: Stone composition Element composition Uric Acid Stone Light Elements (H, C, N, O) Non uric acid stone Heavy Elements (P, Ca, S) Attenuation at 80 kvp Lower HU Higher HU Attenuation at 140 kvp Higher HU Lower HU Calcium 710 HU Uric Acid 290 HU Calcium 480 HU Uric Acid 315 HU 80kV 140kV

Renal Stone Composition: 11 studies (dsdect=8 & ssdect=3) Uric Acid vs. Non UA stone differentiation possible Phantom and humans 100% Reliable for stones 3 mm and above Non-UA subtype of pure composition possible in phantom and in humans mixed composition stones difficult to characterize Stolzman P. Urol Res 2008, Graser A. Invest Radiol 2008, Matlaga B. Urology 2008, Graser A. Eur Radiol 2009, Thomas C. Eur Radiol 2009, Ball D. Radiology 2009,, Hidas G. Radiology 2010, Manglaviti G. AJR 2011, Kulkarni N. JCAT (in-press)

Stone Fragility in Guiding Treatment Heterogenous More fragile to Lithotripsy Homogenous More resistant to lithotripsy CT helps predict stone fragility and susceptibility to lithotripsy Stones which are heterogeneous are more fragile than homogenous stones which are more resistant to ESWL

Stone Precursor-Randall s Plaque Randall s Plaque - Calcium salt deposits in the tip of renal papilla of patients with nephrolithiasis and are potential sites for 30 HU Normal papillae calculus formation These stone bearing papillae appear denser on non-contrast CT and represent Whitish deposits - Randall s plaque Randall s plaque on endoscopy MDCT can help select patients at highrisk for stone formation, who may undergo appropriate medical management to halt the formation of stones Eisner BH et al. J Endourol 2008 58 HU Stone bearing papillae

MDCT in Planning Intervention Simple trigonometry on CT of the patients with complex stones could help endourologists in planning renal access. CT also helps in planning surgical interventions by identifying the location of the posterior calyx thus guiding fluoroscopic procedures like percutaneous nephrolithotomy

Stone Follow up In patients managed medically, CT attenuation is a good predictor of utility of radiography in routine follow up >300 HU Follow up Radiograph <200 HU Follow up CT Calculi with attenuation > 300 HU are radio-opaque & are followed up by Abdominal Radiograph Calculi with attenuation < 200 HU are radiolucent & hence followed up by CT

Stone Follow up Post Intervention Pre Treatment Post Treatment Significant Stone Burden Residual Stone Burden though significantly reduced Significant stone burden necessitates further treatment

Stone vs Stent Abdominal window Bone window Stent Stones Differentiation between stent and stone is vital in post surgical follow up Stents and stones have the same CT appearance on abdominal window. Bone window allows visual distinction between the stent and the stone which is accounted for by differences in pixel density. Tanricut C et al. Urology 2004

MDCT and Radiation Dose A key concern for repeated CT examinations in recurrent stone disease. The effective radiation dose during unenhanced CT 2.8 to 13.1 msv for men / 4.5 to 18 msv for women Techniques for Reduction of Radiation dose - Limit scanning area (not typical Abd+Pelvis exam) - Increase in axial slice thickness to 5mm from 1-3 mm and include 2.5-3 mm coronal reconstructions - Lower dose CT exam ( noise index, kvp, pitch)

Strategies for Dose Reduction Limit Scanning area Increase slice thickness Include coronal reformations + Low kvp DLP 1000 mgy-cm + + Low mas Total Dose Reduction by 40-70% from Standard dose DLP 200 mgy-cm

Ultra-low dose approaches Renal stone Initial scan Standard dose CT (low mas) Follow up scan ultra-low dose CT WT kvp ma Low dose CT <200 lbs 80 75-150 > 200 lbs 100 75-150

Ultra-low dose approaches 177 lbs 280 lbs

IRIS/ASIR/iDOSE/ADIR/SAFIRE FBP VS. Partial IR VS. Full IR Simple Comprehensive Advanced Blend FBP+IR MBIR/Veo Ideal System Few Iterations Advanced model CPU CPU CPU Simple Fast High noise Better IQ Low dose Low noise Optimal IQ Low noise Better resolution

18 DEC 2007 22 DEC 2008 DLP 388 5.82 53% DLP 184 2.76

Radiation Dose-ULD Stone CT 8.8 msv 87% 90% 85% 1.1 2 view KUB Std dose CT ULD CT Wt CTDI msv CTDI msv Category Over all 11.4 8.8 1.8 1.1 < 200 lbs 10.6 8.6 1.3 0.8 > 200 lbs 15.4 10.8 2.3 1.5 Kulkarni N M et al. Radiology 2012

More aggressive dose reduction = 2 View KUB = 0.6 1.2 msv CT KUB = < 1 msv Kulkarni N M et al. Radiology doi:10.1148/radiol.12112470

Author Year Abdomen CT Marin D Radiology. 2010 Prakash P Invest Radiol. 2010 Sagara Y AJR Am J Roentgenol. 2010 Singh S Radiology. 2010 20%- 50% May MS Invest Radiol. 2011 Schindera ST Radiology. 2011 Martinsen AC Eur J Radiol. 2011 Vorona GA Pediatr Radiol. 2011 IQ Dos e

Current Imaging Strategy The scope of imaging has extended beyond the mere detection of stone and its location The current strategy is to determine the stone composition, its fragility and quantification which has great implications in treatment planning

Summary Points MDCT with multiplanar reformations is accurate in stone assessment The qualitative assessment by CT influences management by dictating treatment options like ESWL. Spectral imaging and CAD is emerging for stone composition/quantitation Various stratergies for radiation dose reduction in imaging of urolithiasis achieving accurate diagnosis and reduced radiation dose delivery. New reconstruction algorithms (ASIR) is promising in dose reduction

Thank You Dushyant V Sahani, MD Division of abdominal imaging and intervention Department of Radiology Massachusetts General Hospital White 270, 55 Fruit street Boston, MA-02114 Email:dsahani@partners.org Ph (o): 617-726-8396

References 1. Curhan, G.C., Epidemiology of stone disease. Urol Clin North Am, 2007. 34(3): p. 287-93. 2. Sandhu, C., K.M. Anson, and U. Patel, Urinary tract stones--part I: role of radiological imaging in diagnosis and treatment planning. Clin Radiol, 2003. 58(6): p. 415-21. 3. Ege, G., et al., Acute ureterolithiasis: incidence of secondary signs on unenhanced helical CT and influence on patient management. Clin Radiol, 2003. 58(12): p. 990-4. 4. Heneghan, J.P., et al., Helical CT for nephrolithiasis and ureterolithiasis: comparison of conventional and reduced radiation-dose techniques. Radiology, 2003. 229(2): p. 575-80. 5. Boulay, I., et al., Ureteral calculi: diagnostic efficacy of helical CT and implications for treatment of patients. AJR Am J Roentgenol, 1999. 172(6): p. 1485-90. 6. Fielding, J.R., et al., Unenhanced helical CT of ureteral stones: a replacement for excretory urography in planning treatment. AJR Am J Roentgenol, 1998. 171(4): p. 1051-3. 7. Lin WC, Uppot RN, Li CS, Hahn PF, Sahani DV. Value of automated coronal reformations from 64-section multidetector row computerized tomography in the diagnosis of urinary stone disease. J Urol 2007; 178:907-911; discussion 911. 8. Smith, R.C., et al., Diagnosis of acute flank pain: value of unenhanced helical CT. AJR Am J Roentgenol, 1996. 166(1): p. 97-101. 9. Eisner BH, Iqbal A, Namasivayam S, Catalano O, Kambadakone A, Dretler SP, Sahani DV. Differences in Computed Tomography Density of the Renal Papillae of stone formers and Nonstone formers: A pilot study. J Endourol 2008 Oct 2. 10. Bilen CY, Kocak B, Kiticci G, Danaci M, Sarikaya S. Simple trigonometry on computed tomography helps in planning renal access. Urology. 2007 Aug;70(2):242-5; discussion 245

Jouranal/Yea r DECT Technique # Stones

Dual-Energy CT for Stone Composition Dual Source CT: By operating the two tubes at different energies (80 & 140 kvp) it is effective in tissue material composition 1 2 2 1 Gem stone spectral imaging (single source DECT) - is a recent DE CT operated on rapid kvp switching is also available for tissue characterization/stone composition Stolzman et al Urol Res 2008, Graser et al 2008 Invest Radiol, Graser et al 2009 Eur Radiol, Thomas et al Eur Radiol 2009

Post Processing - DSDCT 80 kv 140 kv 80 140 High and low kvp Two X-ray tube Uric acid stones - Red Non Uric acid stones - Blue (Syngo VA 11; Siemens) 3 material decomposition algorithm

Post Processing - SDCT MD Water MD Iodine High and low kvp Rapid kv twitching Uric Acid stone = MD Water +, MD Iodine Non-Uric Acid stone = MD Water +, MD Iodine + Effective Z Image Effective z number scatter plot

Dual-Energy CT for Stone Composition Phantom Model Uric Acid vs Non uric Acid DSDCT SDCT 65 stones (Size Range- 2-18mm) 35 stones (Size range 3-19mm) MD Water MD Iodine Uric acid Non-Uric acid Uric acid Non-Uric acid Uric acid Non-Uric acid DSDCT (UA -16, Non UA =49) SDCT (UA -6, Non UA =29) <3mm 8/8 (100%) 2/2 (100%) Accuracy >3mm 57/57 (100%) 33/33 (100%) Sensitivity 65/65 (100%) 35/35 (100%)

Dual-Energy CT for Stone Composition Patients Uric Acid vs Non uric Acid DSDCT 37 stones Mean size-6mm, Range 2-24mm) SDCT 49 stones (Mean size-6.8mm, Range 1.2-28mm) CT CT UA 7 Non UA 23 Not Identified 7 Final confirmation - 9/18 patients - 20 Stones (6 uric acid & 14 non uric acid) UA 15 Non UA 34 Not Identified - Final confirmation - 3/17 patients - 8 Stones (All calcium oxalate)

Dual-Energy CT for Stone Composition Phantom Model Differentiation of Non uric Acid DSDCT SDCT Red Blue 1.15 Uric Acid Struvite, Brushite, COM, Cystiene Calculated Effective Z Effective z Uric Acid 6.92 7.2 1.30 Uric acid Struvite 1.45 Uric acid Struvite, Cystine 1.60 Uric acid, Struvite, Brushite, COM, Cystiene Cystine, Brushite COM Brushite COM Struvite 9.72 9.99 Cystine 11.07 11.25 COM 14.37 13.12 90% Cystine stones (9/10) / 84.2% Struvite stones (11/13) 100% Accuracy

Strategies for Dose Reduction Coverage Area From top of diaphragm to lower border of pubic symphysis Restrict Scanning Area From Top of kidneys to base of urinary bladder Dose Reduction by 15-20% Targeted scans focused to area of interest can be performed for follow up CT exams

Strategies for Dose Reduction - Slice Thickness 1-3mm 5mm Increase Slice thickness from 1-3mm to 5mm and include 2.5-3mm Coronal Reformations Dose Reduction by 20-40%

Strategies for Dose Reduction Role of Low kvp - Exam based on Body Weight 140 kv (> 250 lbs) Dose= kvp 120 kv (141-249 lbs) 100/80 kv (<140 lbs) 20% reduction Total 40 % Dose Reduction 20% reduction

Strategies for Dose Reduction- Increase in Noise Index/ reference mas (100-180) Noise Index -15 Noise Index -20 15-20% reduction Noise Index -30 Total 30-40 % Dose Reduction 15-20% reduction

MDCT Protocol Modifications GE WT Slice Th ma NI <300 5 150-450 25- I 16/64- MDCT 30 - F >300 5 150-450 25- I 30 - F NI- Noise index I - Initial scan F- Follow up scan Siemens WT Ref ma 16-64 All wt group 100-160 Sl Thick kv (100-120) DC 5 24x1.2 Pitch 1.2

MDCT Protocol Modifications Review Phase (116 lbs) Monitoring Phase (114 lbs) 61% CTDI- 11.5 CTDI- 4.22

Adaptive Statistical Iterative Reconstruction (ASIR) Noise reduction reconstruction method to improve the signal-to-noise Relies on the accurate modeling of the distribution of noise in the acquired data MGH Experience (GE HD 750) 65 patients studied so far Radiation dose reduction achieved (25-81%) Kole et al 2006 Phys Med Biol