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Manny Don: Tôi sẽ 1) Giới thiệu tổng quan về điện thính giác thân não mở rộng( Stacked ABR) 2) Bàn luận về phương pháp đo và phân tích ABR 3)Điểm qua những nghiên cứu đã công bố và giới thiệu những số liệu của những đề tài nghiên cứu gần đây chưa được công bố với những khối u nhỏ

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  1. Manny Don: Tôi sẽ 1) Giới thiệu tổng quan về điện thính giác thân não mở rộng( Stacked ABR) 2) Bàn luận về phương pháp đo và phân tích ABR 3)Điểm qua những nghiên cứu đã công bố và giới thiệu những số liệu của những đề tài nghiên cứu gần đây chưa được công bố với những khối u nhỏ 4) Đưa ra những biên bản ngắn gọn sàng lọc những khối u nhỏ 5) Những điểm nổi bật nhất của những nghiên cứu mở rộng của Stacked ABR trong tương lai. Talk Outline I. Background: Evolution of the Stacked ABR II. Stacked ABR: Rationale and Method III. Stacked ABR: Studies IV. Tumor Screening Protocol V. Future Stacked ABR Work Talk Outline

  2. Manny Don: Tôi sẽ điểm qua: 1) Khối u dây VIII tự nhiên 2) ABR tiêu chuẩn đánh giá khối u. 3) Giải thích những gì biểu hiện trên ABR tiêu chuẩn. 4) Và thảo luận về các giới hạn của ABR tiêu chuẩn. Background: Evolution of the Stacked ABR A. Eighth Nerve Tumors B. Standard ABR Tumor Detection C. What Do Standard ABR Measures Represent? D. Limitations of Standard ABRs I. Background

  3. Manny Don: First, a brief discussion of eighth nerve tumors Background: Evolution of the Stacked ABR A.Eighth Nerve Tumors B. Standard ABR Tumor Detection C. What Do Standard ABR Measures Represent? D. Limitations of Standard ABRs I. Background

  4. Manny Don: • This is a cross section through a human auditory meatus taken from some work published by Spoendlin and Schrott in 1989. • It shows the spatial relationship of the auditory and vestibular nerve bundles. This relationship is important because acoustic tumors are, in reality, vestibular Schwannomas, i.e. tumors that arise from the Schwann cells of the vestibular nerves. • I want to emphasize that cochleotopic representation in the auditory nerve as deduced from the representation of the turns shown in roman numerals, demonstrates that tumors arising from the vestibular nerves (superior and inferior) can affect auditory nerve fibers from both low and high frequencies. Note, for example that the fibers from turn II representing 1 kHz are, at this level, very close to the inferior vestibular nerve. (2 kHz) (1 kHz) (6 kHz) I. Background: Eight Nerve Tumors HOUSE EAR INSTITUTE Cross Section: Human Auditory Meatus Spoendlin and Schrott (1989)

  5. I. Background: Eight Nerve Tumors HOUSE EAR INSTITUTE Manny Don: For the remainder of the talk, I will be using this schematic drawing of the cross-section through the internal auditory canal (IAC) which shows the four major nerve bundles: the acoustic nerve, the superior and inferior vestibular nerves, and the facial nerve. Cross-section of Internal Auditory Canal (IAC) Sup. Vest. Nerve Facial Nerve Inf. Vest. Nerve Acoustic Nerve

  6. I. Background: Eight Nerve Tumors HOUSE EAR INSTITUTE Manny Don: This is a schematic illustration of how a medium or relatively large tumor arising from the superior vestibular nerve might encroach on the acoustic nerve fibers in the internal auditory canal. Medium or Large Tumor in IAC Sup. Vest. Nerve Facial Nerve Tumor Inf. Vest. Nerve Acoustic Nerve

  7. Manny Don: Next, I would like to review very briefly the standard ABR measures for tumor detection. In a publication a few years ago, Dr. Bauch and his colleagues showed that the best two standard ABR measures for tumor detection was the IT5 and the I-V delay. Background: Evolution of the Stacked ABR A. Eighth Nerve Tumors B.Standard ABR Tumor Detection C. What Do Standard ABR Measures Represent? D. Limitations of Standard ABRs I. Background: Standard ABR

  8. I. Background: Standard ABR HOUSE EAR INSTITUTE Manny Don: IT5 is a measure of the interaural time delay for wave V and was developed many years ago by Selters and Brackmann. One simply compares the latency of wave V between the tumor suspected ear and the non-involved ear. If the latency in the tumor suspected ear exceeds that of the non-involved ear by a certain criterion, the test is positive for a tumor. There is some correction factor for hearing loss. Standard ABR Measures for Acoustic Tumor Detection IT5 = Interaural time delay for wave V 6.4 Non-Tumor Side L1 IT5 =L2 - L1 = 0.9 ms L2 7.3 Tumor Side 0 2 4 6 8 10 12 14 ms

  9. I. Background: Standard ABR HOUSE EAR INSTITUTE Manny Don: The I-V delay is simply the latency difference between wave I and wave V of the ABR response in the suspected ear. If this delay exceeds a certain criterion value, this measure is positive for a tumor. Standard ABR Measures for Acoustic Tumor Detection: I-V Delay = Latency Difference Between Wave I and V I - V = 4.85 ms I-V Delay I-III Delay 6.55 Acoustic Tumor 4.90 1.70 V I III 0 2 4 6 8 10 12 14 ms

  10. Manny Don: Some 20 years ago, we concluded from a study of these two standard ABR measures in a large series of tumor cases, that these measures detected medium and large size tumors but that many tumors smaller than 1 cm would be missed. Studies over the last 10 years have confirmed this finding that standard ABR measures, frequently miss small tumors. “ABR yields high detection scores: up to 90%. The larger the tumor, the easier its detection. It is likely that small tumors (< 1 cm) will be missed.” Eggermont JJ, Don M, Brackmann DE. Electrocochleography and auditory brainstem responses in patients with pontine angle tumors. Ann Otol, Rhinol, and Laryngol, Suppl. 1980; 75: 1-19. I. Background: Standard ABR

  11. Summary of Standard ABR Test Manny Don: In summary of the use of standard ABR measures for detecting acoustic tumors, studies have shown that: (bullet 1) (bullet 2) The consequence of this failure and the advent of Magnetic Resonance Imaging or MRI is that for many clinics… In essence, MRIs are used to screen for acoustic tumors. • Detects nearly all medium and large acoustic tumors. • Misses 30-50% of small (<1 cm)acoustic tumors. Consequence of failure to detect small tumorsAll patients with suspicious clinical hearing and balance symptoms are sent for Magnetic Resonance Imaging (MRI). I. Background: Standard ABR

  12. Manny Don: However, there are some... Drawbacks of Screening with MRI • Relatively expensive ($2100) • Not available everywhere • Invasive, anxiety producing, and uncomfortable test for some patients • Cannot be used on patients with implanted metal devices or materials • Most patients tested do not have a tumor I. Background: Standard ABR

  13. Why do standard ABR measures often fail to detect small tumors ? • The obvious reason:Small tumors exert less pressure and affect a smaller number of neural fibers than larger tumors. • But, these not the only factors because: 1. Many of these small tumors exert enough pressure to cause clinical symptoms. 2. Many small tumors are detected by standard ABR measures. I. Background: Standard ABR

  14. Manny Don: So, the question is,… Our hypothesis is:... Why do standard ABR measures often fail to detect small tumors ? Hypothesis: Standard ABR measures often fail to detect small tumors because these measures are dominated by activity from a subset of 8th nerve fibers that may not be affected by the small tumor. Thus, the limitation is not with ABRs per se, but with the ABR measures used. I. Background: Standard ABR

  15. Manny Don: In order to understand the failure of the standard ABR measures, we need to understand what these measures represent. Background: Evolution of the Stacked ABR A. Eighth Nerve Tumors B. Standard ABR Tumor Detection C. What Do Standard ABR Measures Represent? D. Limitations of Standard ABRs I. Background/What Do Standard ABRs Represent?

  16. Manny Don: (self-explanatory) The IT5 and I-V Delay Use Wave V LatencyMeasures: What does the latency of the ABR wave V represent? I. Background/What Do Standard ABRs Represent?

  17. Manny Don: To begin our discussion of what wave V latency in the ABR represents, I want to clear up ... Two Prevalent Misconceptions About Click-evoked ABRs 1. Clicks have only high-frequency energy. 2. ABRs can only test cochlear function from 2 to 4 kHz. I. Background/What Do Standard ABRs Represent?

  18. I. Background/What Do Standard ABRs Represent? HOUSE EAR INSTITUTE Manny Don: First, let us take a look at the spectral energy of a click. Here we see the amplitude spectrum of a click that is produced by applying a 100 µsec pulse to a TDH-49 earphone. You can see that there is considerable energy from 5 kHz down to at least 200 Hz. Energy falls off above 5 kHz in part because of the response characteristics of the earphone and because of the width of the pulse. We will not discuss this further as there are several technical issues that go beyond the scope of this talk. The point here is that there is considerable low-frequency energy in a click stimulus.

  19. I. Background/What Do Standard ABRs Represent? HOUSE EAR INSTITUTE Manny Don: In this slide we have a series of ABR waveforms. The top trace (white) is the standard ABR obtained with wide -band click stimuli. The succeeding traces represent ABRs from octave wide regions of the cochlea. The center frequencies of these cochlear regions are noted to the left of each trace. I will discuss later how these ABRs from place-specific regions of the cochlea are obtained. Adding these traces together result in the standard ABR waveform shown in the top trace. The main point to see here is that, while the wave V latency of the standard ABR at the top is dominated by cochlear activity from the high frequency regions, there is considerable evoked activity from the lower frequency regions as well. However, this evoked activity from the lower frequency cochlear regions is phase cancelled and only the high-frequency contributions are evident.

  20. I. Background/What Do Standard ABRs Represent? HOUSE EAR INSTITUTE Manny Don: This slide illustrates this point. The top trace is again the standard ABR to wide-band click stimuli. The next two traces are ABRs from octave-wide regions centered at 11.3 and 5.7 kHz. If these two ABRs are added together, the resultant waveform is shown in the bottom trace. Note that the latency as well as the amplitude of the standard ABR at the top is very close to that of the sum of just these two high-frequency ABRs.

  21. Manny Don: Self-explanatory Take Home Messages • A click stimulus is a wideband acoustic signal with as much low-frequency energy as there is high-frequency (HF) energy. • The click-evoked ABR contains neural activity representing all frequency regions of the cochlea, not just the HFs. • In the standard ABR, wave V latency is dominated by HF regions because lower frequency contributions are phase-cancelled. I. Background/What Do Standard ABRs Represent?

  22. Manny Don: Let us now focus on the limitations of the standard ABRs with respect to small tumor detection. Background: Evolution of the Stacked ABR A. Eighth Nerve Tumors B. Standard ABR Tumor Detection C. What Do Standard ABR Measures Represent? D.Limitations of Standard ABRs I. Background/Standard ABRs Limitations

  23. I. Background: Standard ABRs Limitations HOUSE EAR INSTITUTE Manny Don: Let us now represent standard ABR in terms of the auditory nerve fibers in the internal auditory canal or IAC. I am not trying to show the actual distribution of the high-frequency fibers here in the auditory nerve bundle. The important point is that the high-frequency fibers which dominate the wave V latency of the standard ABR measure is only a subset of the fibers in the nerve bundle. Normal Internal Auditory Canal (IAC) Sup. Vest. Nerve Facial Nerve Standard ABR High-frequency Inf. Vest. Nerve Acoustic Nerve

  24. I. Background: Standard ABRs Limitations HOUSE EAR INSTITUTE Manny Don: This illustrates how a large tumor will usually affect a large number of auditory nerve fibers especially those from the high-frequency regions. As a result, the standard ABR measure (latency) is abnormal. Medium or Large Tumor in IAC Sup. Vest. Nerve Facial Nerve Abnormal Standard ABR Tumor Inf. Vest. Nerve Acoustic Nerve

  25. I. Background: Standard ABRs Limitations HOUSE EAR INSTITUTE Manny Don: A small tumor affects fewer fibers but could affect sufficient high-frequency fibers to cause an abnormal standard ABR latency measure. Abnormal standard ABR measures are obtained in about half of the small tumors cases. Small Tumor in IAC Sup. Vest. Nerve Facial Nerve Abnormal Standard ABR Inf. Vest. Nerve Acoustic Nerve

  26. I. Background: Standard ABRs Limitations HOUSE EAR INSTITUTE Manny Don: However, it is easy to see the possibility that a small tumor could affect a small number of fibers that do not include very many high-frequency fibers. As a result, the wave V latency of the standard ABR could still be normal. Our hypothesis is that this is the reason the standard ABR fails to detect many small tumors. Small Tumor in IAC Sup. Vest. Nerve Facial Nerve Normal Standard ABR Inf. Vest. Nerve Acoustic Nerve

  27. Summary • The wave V latency used in standard ABR IT5 and I-V delay measures is dominated by neural activity from high-frequency (HF) regions of the cochlea. • If the tumor does not affect these HF fibers sufficiently, the standard ABR latencies will be normal. • Small tumors do not always affect HF fibers, so they may be missed by standard ABR measures. I. Background/What Do Standard ABRs Represent?

  28. Manny Don: What would be the advantages of developing an ABR measure for tumor screening instead of using the MRI test? Advantages of ABRs over MRIs The ABR is: • Much less expensive • More widely available • Non-invasive • More comfortable than MRI II. Stacked ABR: Rationale

  29. The ChallengeCan we develop an ABR test that: 1. Detects small tumors that cause symptoms, and 2. Significantly reduces the number of patients sent for MRI who do not have a tumor? II. Stacked ABR: Rationale

  30. II. Stacked ABR: Rationale HOUSE EAR INSTITUTE Manny Don: In order to develop an effective ABR test to screen for small tumors, we have to solve this problem where the tumor does not affect the nerve fibers that are critical for the ABR measure. In the case of the standard ABR, the high-frequency subset of fibers. Small Tumor in IAC Sup. Vest. Nerve Facial Nerve Normal Standard ABR High-frequency Inf. Vest. Nerve Acoustic Nerve

  31. Hypothesized that tumor detection fails with standard ABR measures because these measures are dominated by high-frequency activity and small tumors may not always affect the high-frequency fibers. • In order for a new ABR measure to detect small tumors, it must measure activity from essentially all fibers, not just a subset. II. Stacked ABR: Rationale

  32. II. Stacked ABR: Rationale HOUSE EAR INSTITUTE Manny Don: In other words, we need a new ABR measure that is based on essentially all the nerve fibers (encompassed by the black circle), not just a subset. Normal IAC Sup. Vest. Nerve Facial Nerve New ABR Inf. Vest. Nerve Acoustic Nerve

  33. . II. Stacked ABR: Rationale HOUSE EAR INSTITUTE Manny Don: A solution would be to divide the whole auditory nerve into five groups and use the activity from these groups in a new ABR measure. These five groups could represent frequency regions of the cochlea that span the whole frequency range and, therefore, the the whole auditory nerve.

  34. 1 2 3 4 5 Manny Don: An example of a... Diagnostic Test:If you add the activity from each of the five areas, is the amplitude normal? Activity from area 1 + Activity from area 2 + Activity from area 3 + Activity from area 4 + Activity from area 5 Normal Amplitude II. Stacked ABR: Rationale

  35. 1 2 3 4 5 II. Stacked ABR: Rationale HOUSE EAR INSTITUTE Manny Don: Let’s see how this new ABR test would work with the various tumor examples presented earlier: First, in example of the medium or large tumor, we can see that many fibers from areas 2,3, and 4 would be compromised. In addition to the fibers obscured by the tumor, stippled fibers represent fibers that are also affected by the encroaching tumor. Reduction of the contributions from these affected areas would result in an abnormally low overall amplitude of the added activity. Medium or Large Tumor in IAC New ABR: Abnormal Tumor 3 Normal Tumor Acoustic Nerve

  36. 1 2 3 4 5 II. Stacked ABR: Rationale HOUSE EAR INSTITUTE Manny Don: In the case where the small tumor affected sufficient high-frequency fibers to produce an abnormal standard ABR latency measure, it would also reduce the contribution from areas 2 and 3 and produce an abnormally low amplitude of the added activity from all areas. Small Tumor in IAC New ABR: Abnormal Normal Tumor Acoustic Nerve

  37. II. Stacked ABR: Rationale HOUSE EAR INSTITUTE Manny Don: Finally, let’s look at the case where the small tumor did not affect a sufficient number of high-frequency fibers, and therefore, the standard ABR latency measures were normal. Small Tumor in IAC Sup. Vest. Nerve Facial Nerve Normal Standard ABR Inf. Vest. Nerve Acoustic Nerve

  38. 1 2 3 4 5 II. Stacked ABR: Rationale HOUSE EAR INSTITUTE Manny Don: For this troublesome case, the new ABR measure would still be abnormal because the contributions from areas 3 and 4 would be reduced, espcially area 4. Because this new measure involves contributions from essentially all the nerve fibers, it doesn’t matter where the tumor is located or which fibers are affected as long as there has been compromise of a sufficient number of fibers. Small Tumor in IAC New ABR: Abnormal Normal Tumor Acoustic Nerve

  39. Proposed Methods Wideband Click The Derived-band ABR Technique The Stacking Technique II. Stacked ABR: Rationale HOUSE EAR INSTITUTE New ABR Measure Manny Don: This new ABR measure that involves essentially all of the auditory nerve fibers is the Stacked ABR measure. The following is a list of the requirements of such a measure and the proposed methods for fulfilling the requirements. First we need ... Requirements 1. An auditory signal that stimulates essentially all frequency regions of the cochlea 2. A method for separating the responses from different frequency regions of the cochlea 3. A procedure for summing the responses to approximate total neural activity

  40. Stacked ABR: Rationale and Method A. Derived-band ABRs 1. Stimuli a. Clicks b. High-pass masking noise 2. Response subtraction B. Stacking derived-band ABRs C. ABR recordings Manny Don: We begin our Stacked ABR discussion with the derived-band ABR method which fulfills the stimulus requirement and the procedure for separating out activity from different parts of the cochlea, and therefore, different subsets of auditory nerve fibers. The stimuli are clicks and high-pass masking noise. The responses to various combinations of clicks and high-pass noises are subtracted from each other to obtain the derived-band ABRs representing activity initiated from different frequency regions of the cochlea. I’ll demonstrate this later. II. Stacked ABR: Method

  41. TDH-49 II. Stacked ABR: Derived-band ABRs/Stimuli HOUSE EAR INSTITUTE Manny Don: Recall earlier that a click produced by a 100 µsec pulse results in a broad-band stimulus with energy in both high and low frequencies. This spectrum is shown again in the top trace. Thus, when presented at about 60 dB NHL, this click will stimulate most of the cochlea. The traces below show the spectrum of the high-pass masking noise that is used to mask activity from various parts of the cochlea. Click High-pass Masking Noise

  42. II. Stacked ABR: Derived-band ABRs/Response Subtraction HOUSE EAR INSTITUTE Manny Don: Now I would like to demonstrate how we can use click stimuli and high-pass masking noise to obtain ABRs that are related to activity from a specific place and frequency region of the cochlea. In this slide, we see a schematic showing the nerve fibers coming from five regions of the cochlea. The five regions are color-coded and going from left to right, frequency goes from high to low. Shown below is a cross-section of the auditory nerve. When stimulated by a click, essentially all the fibers are activated and the resultant ABR (shown on the right) represents activity from all parts of the cochlea. This is the click-evoked standard ABR with which we all are familiar. I will refer to this as the standard unmasked ABR. ABR to Click Alone (Standard ABR)

  43. II. Stacked ABR: Derived-band ABRs/Response Subtraction HOUSE EAR INSTITUTE Manny Don: If we now present the clicks with 8 kHz high-pass masking noise, the resultant response comes from the unmasked regions of the cochlea, i.e., below 8 kHz. The masked portion, 8 kHz and above, is shown as blackened fibers. ABR to Click + 8 kHz High-pass Masking Noise

  44. ABR to Click Alone (Standard ABR) ABR to Click + 8 kHz High-pass masking noise II. Stacked ABR: Derived-band ABRs/Response Subtraction HOUSE EAR INSTITUTE Manny Don: If we now subtract the 8 kHz masked response from the unmasked response, we obtain a derived-band response. Note that because the activity from below the 8 kHz region is in both the unmasked and 8 kHz masked conditions, this activity is removed by the subtraction process. Thus, the derived-band response represents activity only from above the 8 kHz region. Theoretically, this derived-band activity represents an octave wide region centered at about 11.3 kHz.

  45. Manny Don: Next, if we present the clicks with 4 kHz high-pass masking noise, contributions from 4 kHz and above are removed. Thus, the resultant ABR represents activity from below the 4 kHz region. II. Stacked ABR: Derived-band ABRs/Response Subtraction HOUSE EAR INSTITUTE

  46. ABR to Click + 8 kHz High-pass masking noise II. Stacked ABR: Derived-band ABRs/Response Subtraction HOUSE EAR INSTITUTE Manny Don: If we now subtract the 4 kHz high-pass masked response from the 8 kHz high-pass masked response, we obtain the next derived-band response. By subtraction, the activity below 4 kHz which is common to both the 4 kHz and 8kHz masked response, is removed. The region above 8 kHz is masked in both conditions. Thus, the derived-band response represents activity between 4 and 8 kHz; activity that was unmasked in the 8 kHz condition but masked in the 4 kHz high-pass condition. Theoretically, this derived-band activity represents an octave wide region centered at about 5.7 kHz.

  47. Manny Don: Next, if we present the clicks with 2 kHz high-pass masking noise, contributions from 2 kHz and above are removed. Thus, the resultant ABR represents activity from below the 2 kHz region. II. Stacked ABR: Derived-band ABRs/Response Subtraction HOUSE EAR INSTITUTE

  48. II. Stacked ABR: Derived-band ABRs/Response Subtraction HOUSE EAR INSTITUTE Manny Don: As before, if we now subtract the 2 kHz high-pass masked response from the 4 kHz high-pass masked response, we obtain the next derived-band response. By subtraction, the activity below 2 kHz, which is common to both the 2 kHz and 4k Hz masked responses, is removed. The region above 4 kHz is masked in both conditions. Thus, the derived-band response represents activity between 2 and 4 kHz; activity that was unmasked in the 4 kHz condition but masked in the 2 kHz high-pass condition. Theoretically, this derived-band activity represents an octave wide region centered at about 2.8 kHz.

  49. Manny Don: Summary:... Note that the latency of wave V of the derived-band ABRs increase in latency as the frequency region it represents becomes lower. This progressive delay down the cochlea is the basis for the phase cancellation of the low frequency contributions to the unmasked response. Derived-band ABR Summary • Neural contributions fromdifferent frequency regionsof the cochlea can be obtained using the derived-band ABR method. • Derived-band ABRs represent activity from more specific frequency regions than moderate-to-high level toneburst-evoked ABRs. II. Stacked ABR: Method/Derived ABRs

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