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COMPLEMENTARY AND ALTERNATIVE MEDICINE

Using Ultrasound to Understand Acupuncture Acupuncture Needle Manipulation and Its Effect on Connective Tissue

BY ELISA E. KONOFAGOU AND HELENE M. LANGEVIN

or more than two millennia acupuncture has been a widely accepted method for the treatment of acute and chronic disorders in China. Now, acupuncture is becoming increasingly popular in the West and is routinely recommended for the treatment of pain and for relief from the nausea and vomiting associated with chemotherapy, substance dependency, and chronic disorders difficult to manage with conventional treatment. Nevertheless, as accepted as acupuncture may be as an “alternative” treatment method, the fundamental aspects behind its therapeutic benefits are very poorly understood. Progress in this regard has been further hindered by a consistent discrepancy between traditional theory and scientific explanations. Therefore, an understanding of the mechanism of acupuncture developed through ultrasound-based techniques could play an important role in establishing the validity of this treatment modality in the Western world.

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A New Model for the Therapeutic Effect of Acupuncture

One of the salient features of traditional acupuncture theory is that the needling of acupuncture points causes effects remote from the site of needle insertion and that these effects are mediated via “meridians” running longitudinally along the body surface [1], [2]. Over the past 30 years, most research efforts to elucidate the mechanism of acupuncture have focused on central nervous system effects, presumably resulting from sensory nerve stimulation. This model, however, did not account for the traditional notion that meridians, whose paths are mostly distinct from those of sensory nerves, are key components of acupuncture’s therapeutic effect. Recently, a new model involving connective tissue has been proposed to explain acupuncture’s effect [2]. This model is supported by human and animal experiments that show 1) acupuncture needle manipulation causes mechanical stimulation of connective tissue and 2) the network formed by interstitial or “loose” connective tissue corresponds to the acupuncture meridian network [3]. A new and exciting way to think about acupuncture has consequently emerged: biochemical effects deriving from mechanical stimulation of connective tissue and potential spreading of these effects along connecIEEE ENGINEERING IN MEDICINE AND BIOLOGY MAGAZINE

tive tissue planes may explain acupuncture’s therapeutic effect as well as traditional acupuncture theory. What Is the Needle Doing?

This new focus on meridians and connective tissue has renewed interest in what happens locally in the tissue during acupuncture needle manipulation. Needle manipulation is an important, but mostly overlooked, component of acupuncture therapy; most research to date has used electrical needle stimulation. During traditional acupuncture needling (Figure 1), the acupuncturist performs a series of rapid rotating and pistoning motions while feeling for “needle grasp,” described in ancient Chinese texts as “like a fish biting on a fishing line.” Langevin et al. [1] have shown that this “tug” on the needle is the result of connective tissue winding around the needle during needle rotation, thus creating a mechanical coupling between needle and connective tissue (Figure 2). Subsequent needle movements pull and deform the connective tissue, effectively sending a “mechanical signal” into the tissue. Such a mechanical signal can have a powerful downstream effect on the abundant cells (fibroblast, immune) as well as the neural, vascular, and lymphatic elements present within the connective tissue. Controlling the Movement of the Needle

The biomechanical effect of acupuncture needling on connective tissue is a potentially important component of acupuncture requiring quantitative investigation. A major issue with needle manipulation is that it is difficult to precisely control and quantify the amount of needle movement when the needle is manipulated by hand. To address this problem, Langevin et al. [2] developed a robotic computer-controlled acupuncture needling instrument allowing all movements of the needle to be programmed (Figure 3). Development of the programmable acupuncture needling instrument led to a series of experiments in humans and animals characterizing the effect of needle movement on tissue. These experiments showed that 1) needle rotation has a pronounced effect on the amount of needle grasp, measured as the peak force necessary to pull the needle out of the skin (pullout force) as well as the torque developing at the needle/tissue interface during rotation, 2) needle grasp is not due to a muscle contraction, and 3) pullout force is greater at 0739-5175/05/$20.00©2005IEEE

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Needle manipulation is an important, but mostly overlooked, component of acupuncture therapy.

acupuncture points than at nonacupuncture control points. Therefore, the measurement of needle forces (axial, torque) during needle movement can yield important information on the strength of the bond between the tissue and needle and on the effect of needle manipulation on the bond.

Simply measuring needle force, however, does not give information on tissue stress and strain away from the needle. This is important for a number of reasons: first, measuring how far from the needle tissue biomechanical changes can be detected will allow investigation of whether biomechanical changes are more pronounced along the path of meridians (i.e. connective tissue planes), and second, the measurement of tissue stress/strain induced by needle manipulation will permit translation of in vitro research that combines biomechanical and biochemical measurements, thus giving insights into the biochemical events occurring in the tissue in response to needle manipulation. Role of Ultrasound in the Investigation of Acupuncture

Ultrasound constitutes an ideal medium for evaluating the biomechanical effects of needle manipulation on tissue. Ultrasound has the unique advantage of yielding both images of tissue morphology and biomechanical information. First, in humans,

Fig. 1. After insertion into the forearm of a human volunteer, the needle is rotated until needle grasp is observed. A strong needle grasp may cause tenting of the skin when the needle is pulled back.

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Fig. 2. Winding of connective tissue with acupuncture needle rotation (32 revolutions) (b)–(d) versus insertion without rotation (a) in rat tissue explants. Arrows indicate the needle track. Scale bar, 1 mm.

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Fig. 3. The computer-controlled needling instrument used in the acupuncture experiments.

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Ultrasound has the unique advantage of yielding both images of tissue morphology and biomechanical information.

inserting the acupuncture needle in vivo under sonogram (B-scan ultrasound image) visualization allows identification of anatomical details, i.e., tissue layers (skin, subcutaneous tissue, perimuscular fascia, muscle) penetrated by the needle. Second, continuous ultrasound RF (radio frequency) signal acquisition and processing during acupuncture needle movement (insertion, manipulation, and pullout) permits quantitative tissue motion analysis at a varying distance away from the needle using off-line elasticity imaging techniques [4]. Finally, in vitro high-resolution C-scan ultrasound imaging of animal tissue explants can reveal changes in microscopic tissue structure resulting from acupuncture needle manipulation (Figure 4).

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Fig. 4. Scanning acoustic microscopy of rat subcutaneous tissue at 50 MHz (a) before and (b) after rotation. Scale bar, 1 mm.

Elasticity Imaging

Elasticity imaging is a field that started in ultrasound about 15 years ago. Its aim is to quantify a mechanical response or the mechanical property of tissues resulting from a mechanical stimulus, generated internally or externally. Elasticity imaging’s premise is built on two proven facts: 1) significant differences between mechanical properties of various tissue components exist and 2) the information contained in the coherent scattering, or speckle, is sufficient to depict these differences following an external or internal mechanical stimulus [9]. In breast tissue, for example, not only is the hardness of fat different than that of glandular tissue, but, most importantly, the hardness of normal glandular tissue is significantly different than that of tumorous tissue (benign or malignant) by up to one order of magnitude. This is also the reason why palpation has been proven a reliable tool in the detection of cancer. The second observation is based on the fact that coherent echoes can be tracked while or after the tissue in question undergoes motion and deformation caused by the mechanical stimulus, e.g., an external vibration or a quasi-static compression.

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Fig. 5. The positioning of the ultrasound transducer and needle and graphical descriptions of the needling procedure types. Case 1 corresponds to the example of no needle rotation and 2-mm downward and upward needle movement. Case 2 corresponds to the example of rotation before 2-mm downward and upward movement. Displacement measurements are made between successive ultrasonic frames.

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Elastography [5] is an elasticity imaging technique that uses an externally applied compression and signal processing techniques to track changes in the ultrasonic images before and after compression. By quantifying the motion and amount of deformation as a result of the compression, it has been shown to successfully detect certain types of cancer in humans, especially in the breast and prostate [6], [7]. The technique presented here is

a modification of standard elastography, utilizing merely the motion of the needle (i.e., rotation and pistoning as used in acupuncture) as a stimulus. The amount of motion resulting from the needle motion and the effect on the tissue are imaged at different stages of needle manipulation in order to highlight the effect of needle manipulation on both the tissues directly affected by the needle as well as those at a larger distance but within the ultrasound region of interest. Preliminary Methods and Results

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In vivo ultrasonic imaging using a System FiVe (Vingmed) at 7.5 MHz was performed on the thighs of 12 normal human subjects at different stages of needle motion performed by a computer-controlled acupuncture needling instrument. Disposable stainless steel needles (0.25 mm in diameter) were used. Each subject underwent four separate needling procedures, one at each or four points on the thigh: two distal and two proximal points bilaterally, respectively located 12 and 18 cm proximal to the middle of the patella. Each needling procedure consisted of: 1) needle insertion to a depth of 20 mm, 2) downward and upward 2-mm axial needle movements before rotation, 3) varying amounts of needle rotation (zero, four, eight, and 16 unidirectional revolutions), 4) downward and upward 2-mm axial needle movements after rotation, and 5) needle pullout (Figure 5). Displacements were estimated using the ultrasonic radio-frequency (RF) data, and crosscorrelation techniques were utilized as previously described regarding elastography [4], with a 2-mm window and a window overlap of 60%. Seventy RF scans were acquired continuously during each experiment at the rate of 13.2 frames/s. Ciné-loop displacement images were generated off line during and between the different needle movements.

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Fig. 6. The ultrasound image (s) and displacement images before [Case 1: (a)–(c)] and after [Case 2: (d)–(f)] rotation of 16 revolutions in one human subject during rotation, or lack thereof (left column), during peak downward (or, negative) needle movement (middle column), and peak upward (or, positive) needle movement (right column). The plot (g) shows the variation of the displacement at a point close to the needle in the different cases with time. Note the facilitated detection of the rotation and the existence of a rebound (i.e., a change from negative to positive motion) of the displacement immediately after the downward movement stops in Case 1 (when no needle rotation is applied).

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It was found that soft-tissue displacement could be estimated using only the stimulus caused by the movement of the needle. More importantly, the tissue displacements were found to increase in amplitude by up to tenfold during rotation [Figures 6(d) and (g) and 7(a), (d), and (g)], compared with no rotation [Figure 6(a) and (g)]. Furthermore, needle rotation also was shown to stiffen the tissue, resulting in the absence of tissue reorganization (or, rebound) after downward displacement [Figure 6(g); Figure 7(g)], evident in the case without rotation MARCH/APRIL 2005

Conclusion

Displacement (mm)

[Figure 6(g)], and causing binding of the tissue onto the needle as a result of rotation (corroborating the result shown in Figure 2). It was also noted that rotation of the needle leads to a preferred direction of the tissue motion (horizontal and across the plane of the image shown), especially during downward and upward motion of the needle [Figures 6 and 7, (b)–(c) and (e)–(f)]. This direction conicides with the orientation of the intermuscular fascia [Figure 6(s)]. Figure 8 summarizes the effects of all 12 subjects. Clearly, the rotation displacement increases [Figure 8(a)] and the rebound displacement decreases [Figure 8(d)] with the number of needle rotations. The absolute value of the displacement of the tissue around the needle also increases with both downward [Figure 8(b)] and upward [Figure 8(c)] needle movement. Statistical analysis (repeated measures of ANOVA) showed a significant effect of rotation on tissue displacement during downward rotation (P < 0.001) and upward (P < 0.001) needle motion as well as on rebound tissue motion after downward needle movement (P < 0.05) [8].

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Fig. 7. Displacement images with four revolutions (a)–(c) and eight revolutions (d)–(f) in the same subject as in Figure 6 during rotation (left column), during peak downward (or, negative) needle movement (middle column), and peak upward (or, positive) needle movement (right column). The plot (g) shows the variation of the displacement at a point close to the needle in the two cases with time. Note the facilitated detection of the rotation and the absence of the rebound as a result of the needle rotation.

Tissue displacement caused by acupuncture needle manipulation following needle rotation may deliver a mechanical signal into the subcutaneous tissue and consequently have important effects on cellular elements (fibroblasts, blood vessels, sensory nerves) present within this tissue. This may prove to be the key to acupuncture’s therapeutic mechanism and the proposed imaging technique—the key method for monitoring this effect. Imaging of the displacements occurring before and after rotation at a certain amount of revolutions of the needle allowed for the quantitative analysis of the extent of the tissue affected by the needle when it is rotated, as is the case in the clinical practice of acupuncture. It also allowed for temporal monitoring of the tissue behavior around the needle as a result of the type of needle manipulation. Ongoing investigations over a larger pool of human subjects correlating with biochemical and neurological as well as morphological effects are expected to shed important light on the applications of this technique to better interpret the effect of needling on subcutaneous tissues. Acknowledgments

This study was supported by National Institute of Health grants R21 AT 00300 and R01 AT 01121. Elisa E. Konofagou is currently an associate professor of biomedical engineering and radiology and the director of the Ultrasound and Elasticity Imaging Laboratory at Columbia University. She received her B.S. (Licence) in chemical physics in 1992 from the Université de Pierre et IEEE ENGINEERING IN MEDICINE AND BIOLOGY MAGAZINE

Marie Curie, Paris 6 in Paris, France, and her M.S. in 1993 at the Imperial College of Physics, Engineering and Medicine in Biomedical Engineering. In 1999, she received her Ph.D. in biomedical engineering from the University of Houston for her work in elastography at the University of Texas Medical School in Houston, Texas, and then pursued her postdoctoral work in elasticity-based monitoring of focused ultrasound therapy at Brigham and Women’s Hospital, an affiliate of Harvard Medical School in Boston, Massachusetts. She is also a Member of the IEEE Ultrasonics, Ferroelectrics and Frequency Control and a member of the Acoustical Society of America and the American Institute of Ultrasound in Medicine. Her main interests are in the development of novel elasticity imaging techniques and applications and, more notably, breast elastography, ligament elastography, myocardial elastography, harmonic motion imaging, and focused ultrasound therapy with several close clinical collaborations in the Columbia Presbyterian Medical Center. Helene M. Langevin is currently a research associate professor in the Department of Neurology at the University of MARCH/APRIL 2005

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Fig. 8. Displacements (in the upper left quadrant of the images in Figures 6 and 7) versus measured force during (a) rotation of the needle, (b) downward displacement of the needle, (c) upward displacement of the needle, and (d) rebound of the tissue following the downward displacement. The symbols used in (a) are the same as those in (b), (c), and (d).

Vermont. She received an M.D. degree from McGill University and completed postdoctoral training at the MRC Neurochemical Pharmacology Unit in Cambridge, England, and at Johns Hopkins Hospital in Baltimore, Maryland. She is American Board-certified in internal medicine, endocrinology, and metabolism and is also a licensed acupuncturist in the state of Vermont. For the past four years, she has been conducting research on the mechanism of acupuncture, funded by the National Institutes of Health Center for Complementary and Alternative Medicine.

Address for Correspondence: Elisa Konofagou, Department of Biomedical Engineering, Columbia University, 1210 Amsterdam Ave, ET51 MC 8904, New York, NY 10027 USA. Phone: +1 212 342 0863. Fax: +1 212 342 5773. Email: [email protected]. 46 IEEE ENGINEERING IN MEDICINE AND BIOLOGY MAGAZINE

References [1] H.M. Langevin, D.L. Churchill, J.R. Fox, and M.J. Cipolla, “Mechanical signaling through connective tissue: A mechanism for the therapeutic effect of acupuncture,” FASEB J., vol. 15, no. 12, pp. 2275–2282, 2001. [2] H.M. Langevin, D.L. Churchill, J.R. Fox, G.J. Badger, B.S. Garra, and M.H. Krag, “Biomechanical response to acupuncture needling in humans,” J. Appl. Physiol., vol. 91, no. 6, pp. 2471–2478, 2001. [3] “Relationship of acupuncture points and meridians to connective tissue planes,” Anatomical Record (The New Anatomist), vol. 269, pp. 257–265, 2002. [4] E.E. Konofagou and J. Ophir, “A new method for estimation and imaging of lateral strains, corrected axial strains and Poisson’s ratios in tissues,” Ultrasound Med. Biol.,vol. 24, no. 8, pp. 1183–1199, 1998. [5] J. Ophir, I. Céspedes, H. Ponnekanti, Y. Yazdi, and X. Li, “Elastography: A quantitative method for imaging the elasticity of biological tissues,” Ultrasonic Imaging, vol. 13, no. 2, pp. 111–134, 1991. [6] J. Ophir, S.K. Alam, B. Garra, F. Kallel, E.E. Konofagou, T. Krouskop, and T. Varghese, “Elastography: Ultrasonic estimation and imaging of the elastic properties of tissues,” Proc. Inst. Mech. Engrs., vol. 213, H3, pp. 203–233, 1999. [7] R. Souchon, O. Rouviere, A. Gelet, V. Detti, S. Srinivasan, J. Ophir, and J.Y. Chapelon, “Visualisation of HIFU lesions using elastography of the human prostate in vivo: Preliminary results,” Ultrasound Med Biol., vol. 29, no. 7, pp. 1007–1015, 2003. [8] H.M. Langevin, E.E. Konofagou, G.J. Badger, D.L. Churchill, J.R. Fox, J. Ophir, and B.S. Garra, “Tissue displacements during acupuncture using ultrasound elastography techniques,” Ultrasound Med. Biol., vol. 30, no. 9, pp. 1173–1183, 2004. [9] E.E. Konafagou, “Quo vadis elasticity imaging?” Ultrasonics, vol. 42, no. 1–9, pp. 331–336, 2004.

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