Palpation alone to determine the appropriate needle trajectory is recognized as a contributing factor in the acquisition of non-diagnostic BMTB specimens [1, 2].
CHARLOTTESVILLE, VA, May 20, 2020 — RIVANNA announced that the company was awarded a $1.5M research grant from the National Cancer Institute of the National Institutes of Health to commercialize a low-cost, 3D image-guidance system explicitly designed to facilitate bedside bone marrow and trephine biopsy (BMTB) procedures. The developmental platform, Accuro 3S, will build on patented BoneEnhance® and SpineNav3D™ technologies, designed to automate and improve needle guidance. 3S-series innovation serves to expand the Accuro product line, addressing needs in additional healthcare markets, including orthopedic and emergency and diagnostic medicine.
BMTB is the gold standard for diagnosing and monitoring hematological disorders and malignancies [3, 4]. Although bone marrow biopsies rarely cause serious adverse events [4, 5-7], it is essential to minimize the number of non-diagnostic biopsies as repeated testing delays diagnosis and treatment, consumes additional healthcare resources and causes unnecessary patient anxiety and discomfort [8, 9-11]. Core length from bone marrow biopsy is a critical determinant in making an accurate diagnosis [4, 12, 13]. World Health Organization guidelines recommend that core lengths exceed 1.5 cm. However, multiple studies have reported that 20 – 50% of core lengths are ≤ 1.0 cm [14-19, 12], suggesting that these clinical recommendations are not regularly met.
Two contributing factors in the acquisition of non-diagnostic BMTB specimens are inter-operator variability among healthcare providers and challenging needle placement in obese patients [14-20, 1, 21-22, 12]. These factors stem directly from the difficulty associated with relying on palpable surface anatomical landmarks to guide needle placement to the posterior iliac crest, which may be as deep as 10 cm in obese subjects [1, 2]. Unfortunately, reliance on palpation alone to ascertain the appropriate needle trajectory often results in biopsy retrieval from thin sections of the crest or the sloped surface of the ilium, yielding short trephine [23- 26]. In the absence of bedside image-guidance options, obese patients, and otherwise difficult cases are instead sent to interventional radiology for a high-cost CT-guided procedure [2, 27].
COST-EFFECTIVE IMAGE GUIDANCE
Conversely, ultrasound is a cost-effective image-guidance solution readily deployed at the bedside. It has improved success rates for a wide range of bedside procedures, including soft-tissue biopsy [33-35] and regional anesthesia . However, despite the widespread availability of conventional 2D ultrasound, it has not been investigated for BMTB guidance due to its steep learning curve and the perceived difficulty of interpreting 2D ultrasound images of bone anatomy [25, 28].
RIVANNA’s flagship device, Accuro®, automates ultrasound image detection of spinal landmarks, thereby eliminating conventional ultrasound’s steep learning curve. It guides users to the optimal spinal location and depth for needle placement during neuraxial anesthesia. Unlike conventional ultrasound systems, it enables even novice users to use precise image guidance to augment blind palpation for needle placement [29-30].
“The Accuro spinal navigation device improves the interpretability of boney anatomy within 2D and 3D ultrasound images,” says Will Mauldin, PhD, co-founder and CEO of RIVANNA. “Our intension is to introduce this technology to the hematology/oncology community to help overcome the ultrasound learning curve and extend the proven benefits of real-time ultrasound guidance to patients and practitioners of BMTB procedures.”
The use of an effective bedside guidance solution, such as Accuro 3S, is anticipated to significantly reduce the cost of administering BMTBs due to decreased utilization of interventional radiology services. Of the 660,000 annual BMTB procedures, approximately 160,000 (25%) are performed using CT guidance [2, 31]. According to the 2018 CMS Physician and Hospital Fee Schedules, CT guidance increases the fee of each BMTB procedure by $2900 ($1400 vs. $4300 ). Thus, the added cost borne by US healthcare payers for CT-guidance of BMTB procedures is approximately $480 M each year.
“We’re responding to the clinical need for easy-to-use bedside guidance with 3D bone imaging performance of CT, and automated image interpretation to promote adoption by novice users,” says Mauldin. “We expect this will yield more positive patient outcomes and reduce reliance on high-cost CT-guided procedures following bedside failures.”
1. Konda B, Pathak S, Edwin I, Mishall P, Downie SA, Olson TR, Reed LJ, Friedman EW. Safe and successful bone marrow biopsy: an anatomical and CT-based cadaver study. Am J Hematol. 2014;89(10):943-6. PMID: 24942104.
2. Barnett TT, Reynolds JM, Shakespeare A, Dye P, Rappaport ES, Fang-Hollingsworth Y, Cable CT. A Prospective Comparison of Bone Marrow Biopsy Adequacy with and without Use of Powered Assistive Drill in the Clinical Setting Versus Interventional Radiology. Blood. 2014;124:4823.
3. Parapia LA. Trepanning or trephines: a history of bone marrow biopsy. Brit J Haematol. 2007;139(1):14-9. PMID: 17854303.
4. Bain BJ. Bone marrow trephine biopsy. J Clin Pathol. 2001;54(10):737-42. PMID: 11577117.
5. Bain BJ. Morbidity associated with bone marrow aspiration and trephine biopsy – a review of UK data for 2004. Haematol. 2006;91(9):1293-4. PMID: 16956842.
6. Bain BJ. Bone marrow biopsy morbidity: review of 2003. J Clin Pathol. 2005;58(4):406-8. PMID: 15790706.
7. Bain BJ. Bone marrow biopsy morbidity and mortality. Brit J Haematol. 2003;121(6):949-51. PMID: 12786808.
8. Brunetti GA, Tendas A, Meloni E, Mancini D, Maggiore P, Scaramucci L, Giovannini M, Niscola P, Cartoni C, Alimena G. Pain and anxiety associated with bone marrow aspiration and biopsy: a prospective study on 152 Italian patients with hematological malignancies. Ann Hematol. 2011;90(10):1233-5. PMID: 21287348.
9. Grant RC SF, Abdelhaleem M, Alexander SW, Cada M. Risk factors for inadequate bone marrow biopsies in children. Am J Hematol. 2015;90(9):E187-9; PMID: 26043864.
10. Liden Y, Olofsson N, Landgren O, Johansson E. Pain and anxiety during bone marrow aspiration/biopsy: Comparison of ratings among patients versus healthcare professionals. Eur J Oncol Nurs. 2012;16(3):323-9. PMID: 22341718.
11. Liden Y, Landgren O, Arner S, Sjolund KF, Johansson E. Procedure-related pain among adult patients with hematologic malignancies. Acta Anaesthesiol Scand. 2009;53(3):354-63. PMID: 19243321.
12. Campbell JK, Matthews JP, Seymour JF, Wolf MM, Juneja SK. Optimum trephine length in the assessment of bone marrow involvement in patients with diffuse large cell lymphoma. Ann Oncol. 2003;14(2):273-6. PMID: 12562655.
13. Vardiman JW, Thiele J, Arber DA, Brunning RD, Borowitz MJ, Porwit A, Harris NL, Le Beau MM, Hellstrom-Lindberg E, Tefferi A, Bloomfield CD. The 2008 revision of the World Health Organization (WHO) classification of myeloid neoplasms and acute leukemia: rationale and important changes. Blood. 2009;114(5):937-51. PMID: 19357394.
14. Marinelli LM, Fang H, Howard MT, Hanson CA, Haack JJ, Eick EA, Allen RJ, Ruffridge DE, Byrne CM, King RL. Bone Marrow Biopsy Operator Experience and Impact on Aspirate, Biopsy, and Ancillary Testing Quality. Mayo Clinic Proc. 2018;2(3):241-7. PMID: 30225457.
15. Merzianu M, Groman A, Hutson A, Cotta C, Brynes RK, Orazi A, Reddy V, Teruya-Feldstein J, Amre R, Balasubramanian M, Brandao G, Cherian S, Courville E, Czuchlewski D, Fan G, Grier D, Hoehn D, Inamdar KV, Juskevicius R, Kaur P, Lazarchick J, Lewis MR, Miles RR, Myers JB, Nasr MR, Qureishi HN, Olteanu H, Robu VG, Salaru G, Vajpayee N, Vos J, Zhang L, Zhang S, Aye L, Brega E, Coad JE, Grantham J, Ivelja S, McKenna R, Sultan K, Wilding G, Hutchison R, Peterson L, Cheney RT. Trends in Bone Marrow Sampling and Core Biopsy Specimen Adequacy in the United States and Canada: A Multicenter Study. Am J Clin Pathol. 2018;150(5):393-405. PMID: 30052721.
16. Yang RK, Nazeef M, Patel SS, Mattison R, Yang DT, Ranheim EA, Leith CP. Improving bone marrow biopsy quality through peer discussion and data comparisons: A single institution experience. Int J Lab Hematol. 2018;40(4):419-26. PMID: 29575638.
17. Lynch DW, Stauffer SL, Rosenthal NS. Adequacy of powered vs. manual bone marrow biopsy specimens: a retrospective review of sequential marrow aspirates and biopsies in 68 patients. Am J Clin Pathol. 2015;143(4):535-9. PMID: 25780005.
18. Al-Ibraheemi A, Pham T, Chen L, Syklawer E, Quesada A, Wahed A, Nedelcu E, Nguyen AN. Comparison between 1-needle technique versus 2-needle technique for bone marrow aspiration and biopsy procedures. Arch Pathol Lab Med. 2013;137(7):974-8. PMID: 23808470.
19. Loureiro G, Rizzatti EG, Sandes AF, de Lourdes Chauffaille M. Quality control of bone marrow aspirates: additional steps toward a safer and more efficient procedure. Cancer. 2014;120(9):1441-2. PMID: 24481771.
20. Odejide OO, Cronin AM, DeAngelo DJ, Bernazzoli ZA, Jacobson JO, Rodig SJ, LaCasce AS, Mazeika TJ, Earles KD, Abel GA. Improving the quality of bone marrow assessment: Impact of operator techniques and use of a specimen preparation checklist. Cancer. 2013;119(19):3472-8. PMID: 23921812.
21. Bishop PW, McNally K, Harris M. Audit of bone marrow trephines. J Clin Pathol. 1992;45(12):1105-8. PMID: 1479037.
22. Shaw EB. Ongoing Marrow Adequacy Issue. Arch Path Lab Med. 2015;139(7):846. PMID: 26125423.
23. Hernigou J, Picard L, Alves A, Silvera J, Homma Y, Hernigou P. Understanding bone safety zones during bone marrow aspiration from the iliac crest: the sector rule. Int Orthop. 2014;38(11):2377-84. PMID: 24793788.
24. Hernigou J, Alves A, Homma Y, Guissou I, Hernigou P. Anatomy of the ilium for bone marrow aspiration: map of sectors and implication for safe trocar placement. Int Orthop. 2014;38(12):2585-90. PMID: 24781923.
25. Hirahara AM, Panero A, Andersen WJ. An MRI Analysis of the Pelvis to Determine the Ideal Method for Ultrasound-Guided Bone Marrow Aspiration from the Iliac Crest. Ame J Orthop. 2018;47(5). PMID: 29883505.
26. Attarian S, Reed L, Singh S, Shestopalov A, Singh AP, Budhathoki A, Abi-Aad S, Shah UA, Kim S, Bachiashvili K, Elrafei T, Li W, Yee C, Friedman EW. Visualization of the bone marrow biopsy needle track. Am J Hematol. 2018;93(3):E60-e1. PMID: 29168229.
27. Badiola CM, Scappaticci F, Brahaj D. CT Guided Bone Marrow Aspiration and Core Biopsy. Open J Radiol. 2012;02(02):55-6.
28. Islam A. Ultrasound: a new tool for precisely locating posterior iliac crests to obtain adequate bone marrow trephine biopsy specimen. J Clin Pathol. 2013;66(8):718-20. PMID: 23493477.
29. Priyanka Singla, Adam J Dixon, Jessica L Sheeran, David Scalzo, Frank W Mauldin, Jr, and Mohamed Tiouririne. Feasibility of spinal anesthesia placement using automated interpretation of lumbar ultrasound images: a prospective randomized controlled trial. J Anesth Clin Res. 2019; 10: 878.
30. Daniela Ghisi, Marco Tomasi, Sandra Giannone, Alessandra Luppi, Lucia Aurini, Letizia Toccaceli, Andrea Benazzo, Stefano Bonarell. A randomized comparison between Accuro and palpation-guided spinal anesthesia for obese patients undergoing orthopedic surgery. Reg Anesth Pain Med. 2019 Oct; 2019-100538.
31. Voigt J. The Case of Penny Wise but Access and Quality of Care Foolish. Appl Health Econ Health Policy. 2015;13(2):121-3. PMID: 25761546.
32. Virginia Workers’ Compensation Medical Fee Schedules. Virginia Workers Compensation Commission, 2017.
33. Dogan BE, Dryden MJ, Wei W, Fornage BD, Buchholz TA, Smith B, Hunt K, Krishnamurthy S, Yang WT. Sonography and Sonographically Guided Needle Biopsy of Internal Mammary Nodes in Staging of Patients With Breast Cancer. Am J Roentgenol. 2015;205(4):905-11. PMID: 26397343.
34. Pinkstaff DM, Igel TC, Petrou SP, Broderick GA, Wehle MJ, Young PR. Systematic transperineal ultrasound-guided template biopsy of the prostate: three-year experience. Urology. 2005;65(4):735-9. PMID: 15833518.
35. Youk JH, Kim EK, Kim MJ, Oh KK. Sonographically guided 14-gauge core needle biopsy of breast masses: a review of 2,420 cases with long-term follow-up. Am J Roentgenol. 2008;190(1):202-7. PMID: 18094312.
36. Marhofer P, Chan VW. Ultrasound-guided regional anesthesia: current concepts and future trends. Anesth Analg. 2007;104(5):1265-9, tables of contents. PMID: 17456684.